REAGENTS FOR SIGNAL TRANSDUCTION RESEARCH, Therapeutic Discovery and Preclinical Oncology Aug CATALOG/HANDBOOK 2014 LC Laboratories® Look here firsT TM for: • The Most Important Signaling/Oncology Compounds • The Highest Purities and We reduce product prices whenever possibleabs.com – pleasefor current always prices visit • The Lowest Prices www.LCL

Look here firsT TM for: • > 60 Kinase Inhibitors • Obatoclax • AICAR, Free Base • Okadaic Acid • BafilomycinA 1 – Prices Reduced - (11/13) • Olaparib • Bortezomib – Prices Reduced - (11/13) • Oxaliplatin • Cabazitaxel – Prices Reduced - (6/14) • Paclitaxel • Calyculin A • PD 98059 • Crizotinib – Prices Reduced - (10/13) • PKC412 • Cyclopamine • PMA (Phorbol 12-Myristate 13-Acetate) • Docetaxel • Rapamycin • Doxorubicin • Staurosporine • Everolimus • Temsirolimus • FK-506 • Tofacitinib

Pre cli n ical On colo gy • Foretinib • Trametinib • GDC-0941 • Vemurafenib – Prices Reduced - (6/14) • Gemcitabine • Vinblastine • Lapatinib • Vincristine • Linsitinib – Prices Reduced - (12/13) • Vismodegib • NVP-BEZ235 • Wortmannin

th Our 34 Year Global One-Pricing — our U.S. home 34 1980 – 2014 office ships directly to almost all countries

www.LCLabs.com (800) 937-3720 Outside the U.S.: 1-781-937-0777

• In-stock Products and Sizes are Shipped within

1 Business Day of Order Entry Completion (Subject to Credit Approval)

• Shipped by Next-day Delivery to All U.S. Destinations All shipments to U.S. addresses are automatically sent by overnight service for afternoon arrival. For most packages, the shipping charge is $29.

Our Promise to You We don’t waste your grant/budget funds:

• No T-shirts • No mugs, no pens • No 4-color catalogs or newsletters (very expensive to print!) • No advertisements in journals • No booths at trade shows • No salespeople in the hallways of your institution • No special “Sale” or “Discount” gimmicks • No pricey outside contractors to build our website • No marketing or promotional phone calls to researchers

After all, your grant or budget pays for these components of reagent costs!

Just the Essentials ...

• Important, widely-used compounds

• Highest purities available See the following pages for more about our products and • Lowest prices available their very high purity áand low prices IF you do signal transduction, oncology or other preclinical research,

THEN you have probably been relying on LC Labs products, directly or indirectly, from the time you started your research (unless you started more than ~34 years ago)

In Business for 34 Years - Since 1980, manufacturing and selling directly and through many distributors and other reagent-vendor customers worldwide, LC Laboratories has provided the biomedical research community with some of its most important small-molecule reagents.

Even if you just found our website or catalog today for the first time, you have probably used one or many of our top-quality, widely-used products over the years, via purchases from any of our numerous reagent-vendor customers under their labels (some of these firms have merged or been acquired)*:

• Sigma • Biotrend • Enzo • RBI • Calbiochem • Biovision • Life Technologies • Santa Cruz • Alexis/Axxora • Cascade • LKT Labs • Tocris • Alomone • Cayman • MP Biomedical • Upstate • Anawa • Cell Signaling • Millipore • Wako • Ascent Technology • Molecular Probes • Many Others • Biomol • Chemicon • Promega

Consider the ultimate level of customer testimonials: namely, the enduring confidence in LC Labs that many other reagent vendors — including a number of large, famous, highly reputable firms respected the world over — have demonstrated by buying many hundreds of thousands of vials’ worth of our products during the past 34 years*:

• Bafilomycin A1 • FK-506 • LY 294002 • Staurosporine • Brefeldin A • Forskolin • Okadaic Acid • Thapsigargin • BIM I (GF 109203X) • Genistein • PD 98059 • U0126 • Bryostatin 1 • Gö 6976 • Phorbols (PMA/TPA) • Wortmannin • Calyculin A • H89 • PKC412 • Many Others • Chelerythrine • HA-1077 • Prostratin • Cyclopamine • K252a • Rapamycin • Daidzein • K252c • Resiniferatoxin • Equol • Leptomycin B • SB 202190 • Fasudil • Lestaurtinib • SB 203180

Relying on tens of thousands of publications: not only might you have used LC Labs’ products for many years yourself, you have also undoubtedly relied on data reported in the tens of thousands of publications that used our products, purchased directly from us or under our wholesale customer’s labels, during the past 34 years.

* The company names listed above are respective trademarks owned by the respective companies. LC Laboratories is independent of, and not affiliated with, these companies except to the extent they are or have been customers of LC Laboratories. The information presented here is not intended to imply (i) that any given company listed above has purchased any particular product listed above from LC Laboratories, nor (ii) that LC Laboratories is or has been the sole source of any particular product listed above for any given company listed above. An Unparalleled Record of Innovation for Major Signal Transduction Reagents:

1980 lc Labs becomes the primary worldwide source of high-purity, low-cost PMA (phorbol 12-myristate 13-acetate; TPA), and this has continued without uninterruption for 33 years — more than 150,000 vials sold

1989 lc Labs provides the first high-purity, low-costThapsigargin to the research market

1990 first high-purity, low-costOkadaic Acid

1991 first high-purity, low-costCalyculin A —and we remain the primary worldwide source for this widely-used phosphatase inhibitor

1995 first isomerically pure, low-costG ö 6976

1996 first high-purity, low-costBafilomycin A1

2002 first high-purity, low-costR apamycin

2002 first high-purity, low-costFK -506

2003 first high-purity, low-costLeptomycin B

2004 first high-purity, low-costStaurosporine

2004 first high-purity, low-cost Cyclopamine

2007 LC Labs introduces the first group of high-purity, low-cost major Protein Kinase Inhibitors for prelinical oncology and related research

Continued on next page á Purity and Price Are Not Correlated!

The prices charged by biomedical reagent vendors for a given product tell you nothing about the purity.

For example, as shown in our Purity/Price Comparison Table for Rapamycin (please visit www.LCLabs.com; Cat. No. R-5000) you can pay:

• $173 to Abcam for 1 mg of 98% pure rapamycin

• $235 to R&D Systems for 1 mg of 98% pure rapamycin

• $296.50 to Sigma for 1 mg of 95% pure rapamycin

• $209 to Calbiochem for 1 mg of 98% pure rapamycin

- or -

• $53 to LC Labs for 50 mg of >99% pure rapamycin!

Another example is cyclopamine:

• Among the many cyclopamine suppliers, 19 suppliers charge $18 to $193 for 1 mg; 12 of those suppliers make a purity claim of only 98%, and another 4 claim only 97%

- or -

• LC Labs’ price for 25 mg of >99% pure cyclopamine is $84 — 1/5 to 1/64 of the cost from other major suppliers

Please visit www.LCLabs.com and peruse some of our other Purity/Price Comparison Tables. The picture is clear—price tells you nothing about quality. In Business for 34 Years – Since 1980 Table of Contents

Topic Pages

Biological Activity Index...... i

Disposal Codes...... iv

General Information and Conditions of Sale ...... v

Product Descriptions and Prices...... 1-129

Catalog Number Index...... Inside back cover

Biological Activity Index

Adenylate Cyclase Activators G-4500 Geldanamycin...... 46 F-9929 Forskolin...... 44 G-4177 Gemcitabine, Hydrochloride Salt...... 46 I-5508 imatinib, Methanesulfonate Salt...... 54 Alcohol Dehydrogenase Inhibitors I-5900 ingenol 3-Angelate...... 55 D-2946 Daidzein...... 26 I-4122 irinotecan...... 57 D-7878 Daidzin...... 26 L-4804 lapatinib, Di-p-Toluenesulfonate Salt...... 63 L-6307 Lestaurtinib...... 64 AMP Protein Kinase (AMPK) Activator M-7007 Masitinib, Free Base...... 68 A-1803 A-769662...... 1 M-2433 Mocetinostat, Free Base...... 69 Anthracycline Antibiotics M-5602 Mubritinib, Free Base...... 71 D-4000 Doxorubicin, Hydrochloride Salt...... 33 N-6404 neratinib...... 71 N-8207 Nilotinib, Free Base...... 72 Anti-Cancer Compounds N-9077 Nintedanib, Free Base...... 72 A-6880 17-AAG...... 1 N-4288 nVP-BEZ235, Free Base...... 75 A-3465 alvocidib (Flavopiridol)...... 6 O-5679 OSU-03012, Hydrochloride Salt...... 78 A-1040 ascomycin...... 7 O-7111 Oxaliplatin...... 79 A-1107 Axitinib, Free Base...... 7 P-9600 Paclitaxel...... 80 B-2422 bexarotene...... 10 P-3703 Panobinostat, Free Base...... 80 B-1408 bortezomib, Free Base...... 11 P-6706 Pazopanib, Free Base...... 81 B-1788 Bosutinib, Free Base...... 12 P-8499 PD 184352, Free Base...... 83 B-6697 Bryostatin 1...... 15 P-9688 PD 325901, Free Base...... 83 B-3517 Bryostatin 2...... 15 P-7177 Pemetrexed, Disodium Salt, Heptahydrate...... 84 C-1201 canertinib, Dihydrochloride Salt...... 17 P-6040 Pimecrolimus...... 91 C-2799 Capecitabine...... 17 P-7600 PKC412...... 91 C-2606 ci-994, Free Base...... 21 P-7501 PX-866...... 94 C-8700 Cyclopamine, Free Base...... 24 R-5000 rapamycin...... 96 C-6000 cyclosporin A...... 25 R-7040 Ridaforolimus...... 97 D-3307 Dasatinib, Free Base...... 27 R-1234 roscovitine, Free Base...... 99 D-3440 17-DMAG, Hydrochloride Salt...... 28 S-8906 Saracatinib, Free Base...... 102 D-1000 Docetaxel...... 29 S-8599 Sorafenib, Free Base...... 105 D-3608 Dovitinib, Free Base...... 31 S-8502 Sorafenib, p-Toluenesulfonate Salt...... 106 D-4000 Doxorubicin, Hydrochloride Salt...... 33 S-8877 Sunitinib, Free Base...... 109 E-3866 entinostat, Free Base...... 34 S-8803 Sunitinib, Malate Salt...... 110 E-4506 enzastaurin, Free Base...... 34 T-7802 Tandutinib, Free Base...... 110 E-5500 epothilone B, Free Base...... 36 T-8040 Temsirolimus...... 111 E-4007 Erlotinib, Hydrochloride Salt...... 38 T-2304 Tozasertib, Free Base...... 116 E-4040 everolimus...... 40 T-7310 Tyrphostin AG 1478, Free Base...... 118 F-4900 FK-506...... 42 T-9142 Tyrphostin AG 490...... 118 G-9252 GDC-0941, Free Base...... 44 V-9402 Vandetanib, Free Base...... 119 G-4408 Gefitinib, Free Base...... 45 V-8303 Vatalanib, Dihydrochloride Salt...... 120

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS i LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

V-4050 Vismodegib, Free Base...... 121 Endoplasmic Reticulum Reagents Z-1066 ZSTK474, Free Base...... 128 B-8500 brefeldin A...... 14 Z-9040 Zotarolimus, Free Base...... 128 T-3250 Thapsigargin...... 112 Anti-Neoplastic Compounds Enzyme Activators and Inhibitors (see Anti-Cancer Compounds) (see individual enzyme entries) Apoptosis Reagents ERK Kinase B-8500 brefeldin A...... 14 C-8700 Cyclopamine, Free Base...... 24 (see MEK and MEK Kinases) E-4506 enzastaurin, Free Base...... 34 FLK-1 S-8906 Saracatinib, Free Base...... 102 (see VEGF Receptor Kinase) ATPase Inhibitors Golgi Reagents (See Also Ion channel Reagents — B-8500 brefeldin A...... 14 Ion Co-Transporters) B-1080 bafilomycin A1...... 9 Heat Shock Protein Modulators T-3250 Thapsigargin...... 112 A-6880 17-AAG...... 1 D-3440 17-DMAG...... 28 Calcineurin (See Protein Phosphatase 2B) G-4500 Geldanamycin...... 46 P-3703 Panobinostat, Free Base...... 80 Calcium-Related Reagents Hedgehog Inhibitors Calcium Releasers (from Intracellular Stores) T-3250 Thapsigargin...... 112 Smoothened (Smo) Inhibitors C-8700 Cyclopamine, Free Base...... 24 Ionophores, Calcium V-4050 Vismodegib, Free Base...... 121 I-5700 Ionomycin, Free Acid...... 57 I-6800 ionomycin, Cacium Salt...... 57 Histamine Secretagogues T-3250 Thapsigargin...... 112 Ion Transporter/Co-transporter Inhibitors (Ca2+) Histone Deacetylation Inhibitor (HDAC) T-3250 Thapsigargin...... 112 C-2606 ci-994, Free Base...... 21 E-3866 entinostat, Free Base...... 34 TRPV1 (VR1) Cation Channels M-2433 Mocetinostat, Free Base...... 69 Activators P-3703 Panobinostat, Free Base...... 80 V-8477 Vorinostat...... 124 R-6712 Resiniferatoxin...... 97 T-5096 Tinyatoxin...... 112 Immunosuppressants A-1040 ascomycin...... 7 TRPV4 Cation Channel Activators C-6000 cyclosporin A...... 25 E-4040 everolimus...... 40 (a.k.a. OTRPCH, VR-OAC, TRP12, VRL-2) F-4633 Fingolimod...... 42 P-2170 4α-Phorbol 12,13-Didecanoate...... 86 F-4900 FK-506...... 42 P-8880 4α-Phorbol 12-Myristate 13-Acetate...... 87 P-6040 Pimecrolimus...... 91 R-5000 rapamycin...... 96 Capsaicin-related Reagents R-7040 Ridaforolimus...... 97 R-6712 Resiniferatoxin...... 97 T-8040 Temsirolimus...... 111 T-5096 Tinyatoxin...... 112 T-1377 Tofacitinib, Free Base...... 114 cdc/cdk Kinases Z-9040 Zotarolimus, Free Base...... 128 (see Cell Cycle Reagents) Ion Channel Reagents Cell Cycle Reagents H+-ATPase Inhibitors Cyclin/cdc/cdk Kinase Inhibitors B-1080 bafilomycin A1...... 9 R-1234 roscovitine, Free Base...... 99 Calcium Releasers (from Intracellular Stores) T-3250 Thapsigargin...... 112 CSBP Kinase (see MEK and MEK Kinases) Ionophores, Calcium I-6800 ionomycin, Cacium Salt...... 57 Cyclic Nucleotide Reagents I-5700 Ionomycin, Free Acid...... 57 (see individual entries, e.g. Adenylate Cyclase, Ion Transporter/Co-transporter Inhibitors Guanylate Cyclase, Phosphodiesterase, PKA, (Ca2+) PKC, PKG) T-3250 Thapsigargin...... 112 Cyclin/cdc/cdk Kinases TRPV1 (VR1) Cation Channels (see Cell Cycle Reagents) Activators R-6712 Resiniferatoxin...... 97 EGF Receptor Kinase Inhibitors T-5096 Tinyatoxin...... 112 (see also Tyrosine Kinase Reagents) M-5602 Mubritinib, Free Base...... 71 TRPV4 Cation Channel Activators T-7310 Tyrphostin AG 1478, Free Base...... 118 (a.k.a. OTRPCH, VR-OAC, TRP12, VRL-2) P-2170 4α-Phorbol 12,13-Didecanoate...... 86 P-8880 4α-Phorbol 12-Myristate 13-Acetate...... 87

ii PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

Isoflavones K-2151 K-252a...... 59 K-9609 K-252c...... 60 (see Soybean Isoflavones) S-9300 Staurosporine, Free Base...... 108 JAK-2 Kinase Inhibitors T-9142 Tyrphostin AG 490...... 118 Protein Kinase C (PKC) PKC Activators JAK-3 Kinase Inhibitors T-1377 Tofacitinib, Free Base...... 114 PKC-selective but not PKC Isotype- Kinase Inhibitors, Non-Selective selective Activators P-7600 PKC412...... 91 B-6697 Bryostatin 1...... 15 S-9300 Staurosporine, Free Base...... 108 B-3517 Bryostatin 2...... 15 I-8560 ingenol...... 55 MAP Kinases P-4833 Phorbol 12,13-Dibutyrate...... 86 P-1680 Phorbol 12-Myristate 13-Acetate...... 87 (see MEK and MEK Kinases) P-4462 Prostratin...... 94 MEK and MEK Kinase Inhibitors R-8765 Resiniferonol 9,13,14-Orthophenylacetate...... 97 D-2744 Doramapimod, Free Base...... 29 Negative Controls P-4313 PD 98059...... 82 P-2170 4α-Phorbol 12,13-Didecanoate...... 86 P-8499 PD 184352, Free Base...... 83 P-8880 4α-Phorbol 12-Myristate 13-Acetate...... 87 P-9688 PD 325901, Free Base...... 83 S-1700 SB 202190, Free Base...... 102 PKC Isotype-selective Inhibitors S-3400 SB 203580, Free Base...... 103 E-4506 enzastaurin, Free Base...... 34 U-6770 U0126...... 119 G-6203 Gö 6976...... 50 V-9366 VX-702...... 124 R-9630 rottlerin [See Important Note]...... 99 mTOR Inhibitors PKC Inhibitors not Selective for PKC (see under “T”) or of Unknown Selectivity H-5239 H-89, Dihydrochloride Salt...... 52 Myosin Light Chain Kinase Inhibitors K-2151 K-252a...... 59 W-2990 Wortmannin...... 125 K-9609 K-252c...... 60 P-7600 PKC412...... 91 Neurochemicals S-9300 Staurosporine, Free Base...... 108 R-6712 Resiniferatoxin...... 97 T-5096 Tinyatoxin...... 112 Protein Kinase G (PKG) Inhibitors F-4660 Fasudil, Monohydrochloride Salt...... 40 Nuclear Export Inhibitors H-2330 HA-1077, Dihydrochloride Salt...... 52 L-6100 leptomycin B, Free Acid...... 63 K-2151 K-252a...... 59 Nuclear Localization Inhibitors S-9300 Staurosporine, Free Base...... 108 S-9344 Stauprimide...... 108 Protein Kinase Inhibitors p38 Kinase (see also individual enzymes) (see MEK and MEK Kinases) A-3465 alvocidib (Flavopiridol)...... 6 A-1107 Axitinib, Free Base...... 7 p40 Kinase B-1788 Bosutinib, Free Base...... 12 (see MEK and MEK Kinases) C-1201 canertinib, Dihydrochloride Salt...... 17 D-3307 Dasatinib, Free Base...... 27 PARP Inhibitors D-3608 Dovitinib, Free Base...... 31 (see Poly(ADP-ribose) Polymerase Inhibitors) E-4506 enzastaurin, Free Base...... 34 E-4007 Erlotinib, Hydrochloride Salt ...... 38 Phosphatidylinositol 3-Kinase Inhibitors F-4660 Fasudil, Monohydrochloride Salt...... 40 G-9252 GDC-0941, Free Base...... 44 G-4408 Gefitinib, Free Base ...... 45 L-7962 LY 294002...... 66 G-6055 Genistein...... 48 N-4288 nVP-BEZ235, Free Base...... 75 G-6203 Gö 6976...... 50 P-7050 PIK-75, Hydrochloride Salt...... 89 G-5903 GW2580, Free Base...... 51 P-9050 PIK-90, Free Base...... 90 G-9252 GDC-0941, Free Base...... 44 P-7501 PX-866...... 94 H-5239 H-89, Dihydrochloride Salt...... 52 W-2990 Wortmannin...... 125 H-2330 HA-1077, Dihydrochloride Salt...... 52 I-5508 imatinib, Methanesulfonate Salt ...... 54 PI 3-Kinase K-2151 K-252a...... 59 (see Phosphatidylinositol 3-Kinase Inhibitors) K-9609 K-252c...... 60 K-3351 K-252b...... 60 Platinum-Based Anti-Cancer Compounds K-4651 KT5720...... 60 O-7111 Oxaliplatin...... 79 K-6751 KT5823...... 61 K-7551 KT5926...... 61 Poly(ADP-ribose) Polymerase (PARP) Inhibitors L-4804 lapatinib, Di-p-Toluenesulfonate Salt ...... 63 O-9201 olaparib...... 78 L-6307 Lestaurtinib...... 64 Proteasome Inhibitors L-7962 LY 294002...... 66 B-1408 bortezomib, Free Base...... 11 M-7007 Masitinib, Free Base...... 68 M-5602 Mubritinib, Free Base...... 71 Protein Kinase A (PKA) Inhibitors N-6404 neratinib...... 71 F-4660 Fasudil, Monohydrochloride Salt...... 40 N-8207 Nilotinib, Free Base ...... 72 H-5239 H-89, Dihydrochloride Salt...... 52 N-9077 Nintedanib, Free Base...... 72 H-2330 HA-1077, Dihydrochloride Salt...... 52 O-5679 OSU-03012, Hydrochloride Salt ...... 78

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS iii LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

P-6706 Pazopanib, Free Base...... 81 Soybean Isoflavone-related Compounds P-4313 PD 98059...... 82 P-8499 PD 184352, Free Base...... 83 Soybean Constituents P-9688 PD 325901, Free Base...... 83 A-6900 6"-O-Acetyldaidzin...... 2 P-7600 PKC412...... 91 A-3000 6"-O-Acetylgenistin...... 3 P-7501 PX-866...... 94 A-7860 6"-O-Acetylglycitin...... 3 R-1234 roscovitine, Free Base...... 99 D-2946 Daidzein...... 26 S-8906 Saracatinib, Free Base...... 102 D-7878 Daidzin...... 26 S-1700 SB 202190, Free Base...... 102 G-6055 Genistein...... 48 S-3400 SB 203580, Free Base...... 103 G-5200 Genistin...... 49 S-8599 Sorafenib, Free Base...... 105 G-1152 Glycitein...... 49 S-8502 Sorafenib, p-Toluenesulfonate Salt ...... 106 G-2822 Glycitin...... 50 S-7979 SP600125 ...... 107 M-6730 6"-O-Malonyldaidzin, Free Acid...... 67 S-9300 Staurosporine, Free Base...... 108 M-8090 6"-O-Malonylgenistin, Free Acid...... 67 S-8877 Sunitinib, Free Base...... 109 M-4620 6"-O-Malonylglycitin, Free Acid...... 68 S-8803 Sunitinib, Malate Salt ...... 110 Soybean Isoflavone Metabolites T-7802 Tandutinib, Free Base...... 110 E-5880 (R,S)-Equol ...... 37 T-1377 Tofacitinib, Free Base...... 114 T-2304 Tozasertib, Free Base...... 116 Sphingolipid Reagents T-9142 Tyrphostin AG 490...... 118 F-4633 Fingolimod, Hydrochloride Salt...... 42 T-7310 Tyrphostin AG 1478, Free Base...... 118 U-6770 U0126...... 119 Topoisomerase Inhibitors V-9402 Vandetanib, Free Base...... 119 I-4122 Irinotecan, Hydrochloride Salt, Trihydrate...... 57 V-8303 Vatalanib, Dihydrochloride Salt ...... 120 V-9366 VX-702...... 124 mTOR Inhibitors (Mammalian Target of Rapamycin) W-2990 Wortmannin...... 125 E-4040 everolimus...... 40 Z-1066 ZSTK474, Free Base...... 128 N-4288 nVP-BEZ235, Free Base...... 75 P-6040 Pimecrolimus...... 91 Protein Phosphatase 1 Inhibitors R-5000 rapamycin...... 96 C-3987 Calyculin A...... 16 R-7040 Ridaforolimus...... 97 O-2220 okadaic Acid, Free Acid...... 76 T-8040 Temsirolimus...... 111 O-7519 Okadaic Acid, Potassium Salt...... 77 O-5857 Okadaic Acid, Sodium Salt...... 77 Torkinibs (see mTOR Inhibitors) Protein Phosphatase 2A Inhibitors C-3987 Calyculin A...... 16 TRPV1 (VR1) Cation Channel Activators O-2220 okadaic Acid, Free Acid...... 76 R-6712 Resiniferatoxin...... 97 O-7519 Okadaic Acid, Potassium Salt...... 77 T-5096 Tinyatoxin...... 112 O-5857 Okadaic Acid, Sodium Salt...... 77 TRPV4 Cation Channel Activators Protein Phosphatase 2B (Calcineurin) Reagents (a.k.a. OTRPCH,VR-OAC,TRP12, VRL-2) Inhibitors P-2170 4α-Phorbol 12,13-Didecanoate...... 86 C-6000 cyclosporin A...... 25 P-8880 4α-Phorbol 12-Myristate 13-Acetate...... 87 Related Reagents Tubulin Assembly/Stabilization Promoters A-1040 ascomycin...... 7 D-1000 Docetaxel...... 29 E-4040 everolimus...... 40 E-5500 epothilone B, Free Base...... 36 F-4900 FK-506...... 42 P-9600 Paclitaxel...... 80 P-6040 Pimecrolimus...... 91 VEGF Receptor Kinase Inhibitors R-5000 rapamycin...... 96 A-1107 Axitinib, Free Base...... 7 T-8040 Temsirolimus...... 111 N-9077 Nintedanib, Free Base...... 72 Z-9040 Zotarolimus, Free Base...... 128 P-6706 Pazopanib, Free Base...... 81 Protein Trafficking Reagents B-8500 brefeldin A...... 14 Disposal Codes L-6100 leptomycin B, Free Acid...... 63 A. Suspend or dissolve the compound with a flammable solvent Retinoid Receptor Modulators and incinerate in a chemical incinerator with an afterburner and scrubber. Retinoid X Receptor Modulators B-2422 bexarotene, Free Acid...... 10 Rho-Associated Kinase II Inhibitors F-4660 Fasudil, Monohydrochloride Salt...... 40 H-2330 HA-1077, Dihydrochloride Salt...... 52 RK Kinase (see MEK and MEK Kinases) Smoothened (Smo) Inhibitors C-8700 Cyclopamine, Free Base...... 24 V-4050 Vismodegib, Free Base...... 121

iv PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980 General Information and Conditions of Sale

To Order, Contact: Also, generally, our products are virtually always the highest purity LC LABORATORIES® available, most commonly as measured by HPLC with UV detec- 165 New Boston Street - Woburn, MA 01801 USA tion (these measurements and purity claims do not include residual Tel: (800) 937-3720 solvents or water). Tel (Outside the U.S.): (781) 937-0777 It will occasionally be the case that a few of our prices will not be the lowest compared to those of other vendors on our price comparison Fax: (781) 938-5420 tables for a small number of sizes and/or products of equal purity. But www.LCLabs.com for the vast majority of our products we do indeed offer the highest Email: [email protected] purities at the lowest prices. And, very rarely, there may be cases For each product you wish to order, please specify name, catalog where the purity of a given product is lower than the purity claimed number, unit size and number of vials desired. Our order department by one or more other vendors. is available for telephone orders Monday through Friday, 9:00 a.m. to 5:00 p.m. EST/EDT. Orders may also be placed 24 hours a day Credit Cards via fax or through our web site, www.LCLabs.com. We prefer not to We Accept Mastercard, Visa, American Express, Discover and JCB. receive written confirmation of telephone orders. We are unable to ship our products to individuals not affiliated with an institution or firm. In-Stock Orders Shipped within 1 Business Day Place Orders Directly to Our Woburn Subject to credit requirements and delays related to communications Offices From Almost Any Country in the World such as pro forma invoices or other paperwork needing to be confirmed or resolved, orders for in-stock products are shipped within 1 business Please place all orders directly with our offices in Woburn, MA, using day after the ordering process is completed. the above contact information, except orders for delivery to Australia or Israel, which should be placed with our exclusive distributors in Domestic Order and Shipments those countries. Orders may be placed by phone, fax, ordinary mail or via our web site, Prices and Terms www.LCLabs.com, for shipment to established institutions. Please do not submit orders or Order confirmations via Our prices are effective as of August 1, 2014, F.O.B. Woburn, MA, postal service / email. Shipping and handling charges, insur- NET 30 days (subject to credit approval), and are subject to change ance where appropriate, and any special packaging charges will be without prior notice; please visit www.LCLabs.com for the most prepaid and added to the invoice. Unless otherwise specified, your up-to-date pricing information. This catalog supersedes all previous order will be shipped through UPS or TNT to arrive in the afternoon catalogs. Prices are shown in U.S. Dollars, Euros, Pounds Sterling of the following day. Next day air services are also available through and Japanese Yen. Federal Express and other carriers; additional charges will apply. We Purity Designations do not offer ground or second day air shipment. Specification Test Result Range Sales and Shipments Outside the U.S. > 99.5% 99.45 - 99.99% Place orders directly to our U.S. headquarters in Woburn, MA, USA > 99% 99.01 - 99.99% from any country in the world except Australia and Israel, in any of 99% 98.75 - 99.99% four currencies: US Dollars, Euros, Pounds Sterling and Japanese > 98.5% 98.45 - 99.99% Yen, as shown in the price list. Orders from most countries (other > 98% 98.01 - 99.99% than Japan and most members of the European Union) must be paid by credit card at the time of ordering or in advance by check or wire in U.S. Dollars. Because of the extra work and costs for shipping We presently do not sell any catalog-numbered products that test and preparations for customs transit, we must add additional handling lower than 98.01%, except for rare cases where slight instability or charges for international shipments. These charges do not include the other purification problems necessitate a lower purity specification. cost of shipment by our choice of TNT, UPS or Federal Express. If Also, we do occasionally sell compounds of lower than 98% purity, you choose a different carrier, additional charges may apply. Please but only by special arrangement on a case-by-case basis and never clearly specify your choice of carrier when your order is placed. We under our regular catalog numbers. will choose an appropriate customs broker for import clearance unless you specify your preferred choice at the time your order is placed. All The Highest Purity and the Lowest Prices duties, tariffs, taxes, and broker fees must be paid by the customer. We advertise our products as having, “The highest purity and the lowest prices.” No Ice Needed During Shipping Generally, the prices of each size of each of our products are lower Although many of our products require storage at -20 oC for optimal than the prices charged by other vendors whose products and public long-term stability, all of our products are stable for at least several information policies conform to the criteria set forth in our price weeks at ambient temperatures. Thus, all products are shipped at comparison tables (please view any table selected from the list at ambient temperature without risk of degradation; there is no need for http://www.lclabs.com/PriceComparisonsbyAlpha.php4.) blue ice or dry ice during shipment of any of our products.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS v LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Exclusive Distributors Material Safety Data Sheets and Certificates Our main office in Woburn, MA, USA accepts orders from all of Analysis countries in the world except Australia and Israel. For shipments to Material Safety Data Sheets and Certificates of Analysis for the these two countries, please order from our exclusive distributors: compounds that LC Laboratories® offers for sale are available at www.lclabs.com. Australia Scientifix Pty Ltd Use of Our Products ABN: 81083311853 The compounds are for research use only, and are not for human, PO Box 18 veterinary, food or household use. These products may be covered Southland Centre by composition-of-matter, use, or process patents. No license under Cheltenham, Victoria, 3192 any patent is granted or implied. We assume no liability for dam- Australia ages or penalties resulting from use of the information or products Free Call: 1800 007 900 provided herein, nor should a listing of any product or description of (Australian Residents Only) use be construed as a license to operate under, or a recommendation Phone: +61 3 8540 5900 to infringe, any patent. Fax: +61 3 9548 7177 Email: [email protected] Warranties Web: www.scientifix.com.au We warrant that our products, at the time of shipment, conform to the descriptions as provided in our catalog, analytical information Israel report, or other literature, if furnished to Buyer. THIS WARRANTY Bar-Naor Ltd. IS EXCLUSIVE, AND LC LABORATORIES® MAKES NO OTHER P.O. Box 6877 WARRANTY, EXPRESSED OR IMPLIED, INCLUDING ANY Ramat-Gan, 52170 IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS Israel FOR ANY PARTICULAR PURPOSE. Phone: 03-618-3957 Fax: 03-760-0641 Since we cannot be certain of your handling, storage or application Mobile: 050-6890-875 of our chemicals, we offer no warranties regarding use, and will not Email: [email protected] be responsible for any loss involving their use. Web: www.barnaor.com Our sole and exclusive liability with respect to any product proved to our satisfaction (within one year of purchase) to be defective shall Minimum Order be the replacement of such products without charge, or refund of the There is no minimum order; all requests for our products are purchase price, at our sole discretion, upon the return of such products ® welcomed. in accordance with our instructions. LC LABORATORIES SHALL NOT BE LIABLE FOR ANY INCIDENTAL, CONSEQUENTIAL, Quantity Discounts OR CONTINGENT DAMAGES. Larger quantities of listed compounds are usually available at sig- nificant discounts. Please contact us for more information.

Returns Please inspect all shipments immediately upon arrival. In the event of any damage or discrepancy, please inform us immediately. Goods may not be returned for credit except with our authorization and in compliance with our return shipment instructions. If the reason for return is not our fault, a 25% restocking charge will apply.

vi PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980 Alphabetical Listing of Products and Prices

proteolytic components of the 26S proteasome by an AMPK- 29060-LE — see Vinblastine, Sulfate Salt (Cat. No. V-7300 on page 121). independent mechanism.” FEBS Lett. 582: 2650-2654 (2008). • Sold for laboratory or manufacturing purposes only; not for 9CI — see Ridaforolimus (Cat. No. R-7040 on page 97). human, medical, veterinary, food, or household use. A-1803 A-769662, >99% • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Size US$ ¤ £ ¥ Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 10 mg 70 52 45 5,500 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 25 mg 162 121 104 12,600 and other common law exemptions of Canadian patent law; (vi) 50 mg 297 222 190 23,200 Section 68B of the Patents Act of 1953 in New Zealand together 100 mg 510 381 327 39,800 with the amendment of same by the Statutes Amendment Bill of 200 mg 765 571 490 59,700 2002; (vii) such related legislation and/or case law as may be or 300 mg 1075 802 689 83,900 become applicable in the aforementioned countries; and (viii) such 500 mg 1635 1220 1048 127,600 similar laws and rules as may apply in various other countries. NOTE: Euro, Pound and Yen prices are revised regularly. • Not available in some countries; not available to some institutions; Please visit www.LCLabs.com for our current prices. not available for some uses.

M.W. 360.39 c20H12N2O3S [844499-71-4] N Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 33 mg/mL; soluble in ethanol at 5 mg/mL with HO slight warming; very poorly soluble in water; maximum O OH solubility in plain water is estimated to be about 50-100 N µM; buffers, serum, or other additives may increase or H decrease the aqueous solubility. Disposal: A S • A-769662 is a potent, reversible activator of AMP-activated A-6880 17-AAG, >99% protein kinase (AMPK). AMPK is an heterotrimer and αβγ Synonyms: [17-(Allylamino)geldanamycin] plays an important role in regulating cellular and whole-body metabolism. A-769662 only activates AMPK heterotrimers [17-(Allylamino)-17-demethoxygeldanamycin] A-1803-2009-10-08-kedREV.SKC containing the β1 subunit. A-769662 activates AMPK through the [Tanespimycin] β subunit carbohydrate-binding module and the γ subunit but not the AMP-binding sites. Scott, J.W. et al., “Thienopyridone drugs Size US$ ¤ £ ¥ are selective activators of AMP-activated protein kinase beta1- 25 mg 42 30 27 3,200 containing complexes.” Chem. Biol. 15: 1220-1230 (2008). 100 mg 87 63 55 6,700 • A-769662 stimulated partially purified rat liver AMPK with an 200 mg 154 112 97 11,800 EC50 of 0.8 µM and inhibited fatty acid synthesis in primary rat 250 mg 183 133 116 14,100 hepatocytes with an IC50 of 3.2 µM. A-769662 decreased liver 500 mg 248 180 157 19,100 malonyl CoA levels of Sprague Dawley rats and the respiratory 1 g 425 308 269 32,700 exchange ratio, VCO2/VO2, and thus increased rate of whole- 2 g 728 527 461 55,900 body fatty acid oxidation. A-769662 reduced hepatic expression of 5 g 1185 858 750 91,100 PEPCK, G6Pase, and FAS, decreased body weight gain, lowered plasma glucose by 40%, and reduced both plasma and liver 10 g 1890 1369 1197 145,200 NOTE: Euro, Pound and Yen prices are revised regularly. triglyceride levels in ob/ob mice. Cool, B. et al., “Identification Please visit www.LCLabs.com for our current prices. and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic M.W. 585.69 c31H43N3O8 [75747-14-7] syndrome.” Cell Metab. 3: 403-416 (2006). Warning: Toxic. • A-769662 induces allosteric activation of AMP-activated protein Storage: Store at or below -20 °C. Solubility: Soluble kinase (AMPK) and inhibition of dephosphorylation of AMPK in DMSO at 150 mg/mL; soluble in ethanol at 5 mg/mL; on Thr-172, similar to the effects of AMP. Sanders, M.J. et al., very poorly soluble in water; maximum solubility in plain “Defining the mechanism of activation of AMP-activated protein water is estimated to be about 20-50 µM; buffers, serum, kinase by the small molecule A-769662, a member of the or other additives may increase or decrease the aqueous thienopyridone family.” J. Biol. Chem. 282: 32539-32548 (2007). solubility. Disposal: A • The effects of A-769662 are not dependent on the upstream kinase • Synthetic derivative of geldanamycin (Cat. No. G-4500 used in intact cells. Göransson, O. et al., “Mechanism of action of on page 46) demonstrating greater stability and lower in A-769662, a valuable tool for activation of AMP-activated protein vivo toxicity than its parent compound. 17-AAG binds kinase.” J. Biol. Chem. 282: 32549-32560 (2007). specifically to heat shock protein Hsp90 in a manner similar • In skeletal muscle, A-769662 activates β1-containing AMPK to geldanamycin, but the binding is weaker. Schulte, T.W. complexes, but induces glucose uptake via a PI3 kinase-dependent and Neckers, L.M., “The benzoquinone ansamycin pathway. Treebak, J.T. et al., “A-769662 activates AMPK β1- 17-allylamino-17-demethoxygeldanamycin binds to Hsp90 containing complexes but induces glucose uptake through a PI3 and shares important biologic activities with geldanamycin.” kinase-dependent pathway in mouse skeletal muscle.” Cancer Chemother. Pharmacol. 42: 273‑279 (1998). Am. J. Physiol. Cell Physiol. (2009). • Inhibits Akt activation and HER2 expression in tumor cells. • A-769662 inhibits 3T3-L1 adipocyte differentiation and may Basso, A.D. et al., “Ansamycin antibiotics inhibit Akt activation be used to treat obesity. Zhou, Y. et al., “Inhibitory effects of and cyclin D expression in breast cancer cells that overexpress A-769662, a novel activator of AMP-activated protein kinase, on HER2.” Oncogene 21: 1159‑1166 (2002). 3T3-L1 adipogenesis.” Biol. Pharm. Bull. 32: 993-998 (2009). • Exhibits 100-fold higher binding affinity for tumor-cell-derived • A769662 inhibited the function of the 26S proteasome via an Hsp90 over that derived from normal cells. Kamal, A. et al., “A AMPK-independent mechanism. Moreno, D. et al., “A769662, high-affinity conformation of Hsp90 confers tumour selectivity on a novel activator of AMP-activated protein kinase, inhibits non- Hsp90 inhibitors.” Nature 425: 407‑410 (2003).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 1 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Sensitizes tumor cells to growth arrest and apoptosis induced by paclitaxel (Cat. No. P-9600 on page 80). A-6900 6"-O-Acetyldaidzin, >98% Nguyen, D.M. et al., “Sequence-dependent enhancement Synonyms: [Daidzin 6''-O-Acetate] of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin.” Size US$ ¤ £ ¥ J. Thorac. Cardiovasc. Surg. 118: 908‑915 (1999) and 1 mg 66 46 40 6,200 Solit, D.B. et al., “Inhibition of heat shock protein 90 function 5 mg 185 129 112 17,500 down-regulates Akt kinase and sensitizes tumors to Taxol.” 10 mg 315 220 191 29,700 Cancer Res. 63: 2139‑2144 (2003). 25 mg 550 383 333 51,900 • Sensitizes colon cancer cells to cisplatin-induced cell death. NOTE: Euro, Pound and Yen prices are revised regularly. Vasilevskaya, I.A. et al., “Quantitative effects on c-Jun N-terminal Please visit www.LCLabs.com for our current prices. protein kinase signaling determine synergistic interaction of M.W. 458.41 c H O [71385-83-6] cisplatin and 17-allylamino-17-demethoxygeldanamycin in colon 23 22 10 cancer cell lines.” Mol Pharmacol. 65: 235‑243 (2004). Storage: Store desiccated at or below -20 °C. Solubility: Soluble in DMSO, methanol or ethanol. • Inhibits angiogenesis. Kaur, G. et al., “Antiangiogenic properties Disposal: A of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator.” • Isoflavone derivative found in soy-based food products. Wang, H. Clin. Cancer Res. 10: 4813‑4821 (2004). and Murphy, P.A., “Isoflavone content in commercial soybean • Sold for laboratory or manufacturing purposes only; not for foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). human, medical, veterinary, food, or household use. • See the extensive comments before the listing for Genistein (Cat. No. G-6055 on page 48). O • STABILITY: Very little information about the stability of this NH H C O compound is available at present. In our experience, when stored 2 CH in the dry state, frozen and desiccated, this compound has retained 3 NH its original purity for several years. We have been informed O that aqueous or alcoholic solutions can undergo substantial H C H 3 decomposition less than a day after being prepared, particularly H C O O 3 H C O CH if they are held at room temperature. We recommend that this 3 3 product be stored in bulk in the dry state, with a desiccant, at H C 3 the coldest available temperature. Small working quantities of OCONH solutions should be made up just prior to use. 2 • Aqueous solutions of this compound are somewhat unstable, AB-1010 — see Masitinib, Free Base (Cat. No. M-7007 on page 68). particularly at room temperature; several percent decomposition can occur in 12-24 hours. For quantitative work, standard solutions ABT-578 — see Zotarolimus, Free Base (Cat. No. Z-9040 on page 128). should be made fresh daily. AC010220 — see Quizartinib, Free Base • The 1 mg size (+ ca. 2-3%) consists of a film adhering to the walls (Cat. No. Q-4747 on page 95). of the ampule and cannot be easily subdivided by weighing. The larger sizes contain a weighable powder. AC220 — see Quizartinib, Free Base (Cat. No. Q-4747 on page 95). • The 98% purity figure may include small amounts of acetyl Acadesine — see AICAR, Free Base (Cat. No. A-1098 on page 5). monoesters other than the 6"-isomer. • See also these related products: - Daidzein (Cat. No. D-2946 on page 26). Novel Acetylated Forms - Daidzin (Cat. No. D-7878 on page 26). of the Soybean Isoflavones - 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). Only in recent years has it been recognized that large and variable • Sold for laboratory or manufacturing purposes only; not for portions of the total daidzein, genistein and glycitein found in certain soy human, medical, veterinary, food, or household use. products, especially those processed with heating, toasting and/or high pH, OH occur in the 6"-O-acetyl forms, not as the free glycosides or aglycones. O O

Because these compounds have only recently been found in soybean O products, their specific biological, pharmacological and nutritional proper- ties have not been extensively investigated. Given the increasing use of soy O O O products and the many beneficial nutritional properties attributed to the OH isoflavone components of those soy products, it appears that further stud- HO ies of the biological role of these novel soy isoflavones are of substantial HO scientific and medical importance. Acetyldinaline — see CI-994, Free Base LC Laboratories® offers the three acetylated isoflavones from soybeans: (Cat. No. C‑2606 on page 21). 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2), 6"-O-Acetylgenistin (Cat. No. A-3000 on page 3) and 6"-O-Acetylglycitin (Cat. No. A-7860 on page 3).

2 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

A-3000 6"-O-Acetylgenistin, >98% A-7860 6"-O-Acetylglycitin, >98% Synonyms: [Genistin 6''-O-Acetate] Synonyms: [Glycitin 6''-O-Acetate]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 1 mg 59 41 36 5,600 1 mg 74 52 45 7,000 5 mg 168 117 102 15,900 5 mg 195 136 118 18,400 10 mg 280 195 170 26,400 10 mg 330 230 200 31,100 25 mg 525 366 318 49,500 25 mg 585 408 354 55,200 NOTE: Euro, Pound and Yen prices are revised regularly. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Please visit www.LCLabs.com for our current prices.

M.W. 474.71 C23H22O11 [73566-30-0] M.W. 488.44 c24H24O11 [134859-96-4] Storage: Store desiccated at or below -20° C. Storage: Store desiccated at or below -20 °C. Solubility: Soluble in DMSO, methanol or ethanol. Solubility: Soluble in DMSO, methanol or ethanol. Disposal: A Disposal: A • Isoflavone derivative found in soy-based food products. Wang, H. • Isoflavone derivative found in soy-based food products. Wang, H. and Murphy, P.A., “Isoflavone content in commercial soybean and Murphy, P.A., “Isoflavone content in commercial soybean foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). • See the extensive comments before the listing for Genistein • See the extensive comments before the listing for Genistein (Cat. No. G-6055 on page 48). (Cat. No. G-6055 on page 48). • STABILITY: Very little information about the stability of this • STABILITY: Very little information about the stability of this compound is available at present. In our experience, when stored compound is available at present. In our experience, when stored in the dry state, frozen and desiccated, this compound has retained in the dry state, frozen and desiccated, this compound has retained its original purity for several years. We have been informed its original purity for several years. We have been informed that aqueous or alcoholic solutions can undergo substantial that aqueous or alcoholic solutions can undergo substantial decomposition less than a day after being prepared, particularly decomposition less than a day after being prepared, particularly if they are held at room temperature. We recommend that this if they are held at room temperature. We recommend that this product be stored in bulk in the dry state, with a desiccant, at product be stored in bulk in the dry state, with a desiccant, at the coldest available temperature. Small working quantities of the coldest available temperature. Small working quantities of solutions should be made up just prior to use. solutions should be made up just prior to use. • Aqueous solutions of this compound are somewhat unstable, • Aqueous solutions of this compound are somewhat unstable, particularly at room temperature; several percent decomposition particularly at room temperature; several percent decomposition can occur in 12-24 hours. For quantitative work, standard solutions can occur in 12-24 hours. For quantitative work, standard solutions should be made fresh daily. should be made fresh daily. • The 1 mg size (+ ca. 2-3%) consists of a film adhering to the walls • The 1 mg size (+ ca. 2-3%) consists of a film adhering to the walls of the ampule and cannot be easily subdivided by weighing. The of the ampule and cannot be easily subdivided by weighing. The larger sizes contain a weighable powder. larger sizes contain a weighable powder. • See additional comments about acetyl isoflavones above the entry • See additional comments about acetyl isoflavones above the entry for 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). for 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). • The 98% purity figure may include small amounts of acetyl • The 98% purity figure may include small amounts of acetyl monoesters other than the 6"-isomer. monoesters other than the 6"-isomer. • See also these related products: • See also these related products: - Genistein (Cat. No. G-6055 on page 48). - Glycitein (Cat. No. G-1152 on page 49). - Genistin (Cat. No. G-5200 on page 49). - Glycitin (Cat. No. G-2822 on page 50). - 6"-O-Malonylgenistin (Cat. No. M-8090 on page 67). - 6"-O-Malonylglycitin (Cat. No. M-4620 on page 68). • Another CAS number previously assigned to acetylgenistin, • Sold for laboratory or manufacturing purposes only; not for namely 380614-26-6, has been deleted by CAS and is no longer in human, medical, veterinary, food, or household use.

use. OH • Sold for laboratory or manufacturing purposes only; not for O O A-3000 human, medical, veterinary, food, or household use. MeO O OH O OH O O O O

O OH HO O O O HO

OH Adeo — see (R,S)-Rolipram (Cat. No. R-2020 on page 98). HO OH Adriacin — see Doxorubicin, Hydrochloride Salt (Cat. No. D-4000 on page 33) and see its active ingredient, namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). Adriamycin — see its active ingredient, namely Doxorubicin, Hydrochloride Salt (Cat. No. D-4000 on page 33) and Doxorubicin, Free Base (Cat. No. D-4099 on page 32). Adriblastin — see Doxorubicin, Hydrochloride Salt (Cat. No. D-4000 on page 33) and see its active ingredient, namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 3 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

tyrosine kinase inhibitor for the treatment of solid tumors.” Adriblastina — see Doxorubicin, Hydrochloride Salt (Cat. No. D-4000 on page 33) and see its active ingredient, Curr. Opin. Investig. 9: 1336‑1346 (2008). namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). • Afatinib is the active ingredient in the drug product sold under the trade names Gilotrif® in the US (previously Tomtovok®) A-8644 Afatinib, Free Base, >99% and Giotrif® in Europe (previously Tovok®). This drug is Synonyms: [BIBW-2992] approved in much of the world (including the United States, Canada, the United Kingdom, and Australia) for the treatment Related Terms: [Gilotrif] [Giotrif] [Tomtovok] [Tovok] of metastatic non-small cell lung carcinoma. NOTE: THE Size US$ ¤ £ ¥ AFATINIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT Gilotrif®, Giotrif®, 10 mg 39 29 25 3,800 TOMTOVOK® nor TOVOK® AND IS NOT FOR HUMAN 25 mg 73 55 47 7,000 USE. 50 mg 125 94 81 12,000 • Chemical Abstracts Service currently has two different CAS 100 mg 199 149 128 19,200 numbers for afatinib. One of them, 439081-18-2, is by far the 200 mg 348 261 224 33,500 most widely used, but its entry in the CAS database does not show 500 mg 689 517 444 66,300 the geometry of the double bond. A later CAS number, 850140- 1 g 1160 870 748 111,600 72-6, is not in wide use, but its entry in the CAS database shows 2 g 1690 1267 1090 162,600 the trans geometry of the double bond. It is likely that CAS will NOTE: Euro, Pound and Yen prices are revised regularly. eventually cancel one of these two numbers. Please visit www.LCLabs.com for our current prices. • Related CAS numbers: 850140-73-7 for the afatinib dimaleate salt. M.W. 485.94 c24H25ClFN5O3 [850140-72-6] • Another CAS number previously assigned to afatinib, namely [439081-18-2] 915958-11-1, has been deleted by CAS and is no longer in use. Storage: Store at or below -20 ºC. Solubility: Soluble in • Sold for laboratory or manufacturing purposes only; not for DMSO at 200 mg/mL; soluble in ethanol at 25 mg/mL; human, veterinary, food, or household use. very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 µM; buffers, serum, • This product is offered for R&D use in accordance with (i) 35 or other additives may increase or decrease the aqueous USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese solubility. Disposal: A Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Afatinib, also known as BIBW-2992, is an irreversible dual Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 and other common law exemptions of Canadian patent law; (vi) (HER2) tyrosine kinases. Section 68B of the Patents Act of 1953 in New Zealand together • Afatinib inhibits EGFR1 tyrosine kinase (IC50 = 0.5 nM) and with the amendment of same by the Statutes Amendment Bill of EGFR2 (HER2) tyrosine kinase (IC50 = 14 nM). It also suppresses 2002; (vii) such related legislation and/or case law as may be or EGF-induced EGFR phosphorylation and cellular proliferation in become applicable in the aforementioned countries; and (viii) such various cell lines, including EGFR-overexpressing and HER2- similar laws and rules as may apply in various other countries. expressing cell lines A431, NIH-3T3-HER2, NCI-N87 and • Not available in some countries; not available to some institutions; BT-474. Oral afatinib induced tumor regression in mice carrying not available for some uses. A431 or MDA-MB-453 xenografts. Both xenografts are EGFR- overexpressing and HER2-expressing. Afatinib also showed O N O inhibitory effects in NCI-N87 gastric and SKOV-3 ovarian models. N CH NH Eskens, F.A. et al., “A phase I dose escalation study of BIBW 3 2992, an irreversible dual inhibitor of epidermal growth factor N N H C O H receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 3

2-week off schedule in patients with advanced solid tumours.” F Br. J. Cancer 98: 80-85 (2008). Cl • Afatinib inhibits the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Afinitor — see Everolimus (Cat. No. E-4040 on page 40). Afatinib suppressed proliferation of cancer cell lines and caused tumor regression in xenograft and transgenic lung cancer models, AG 1478 — see Tyrphostin AG 1478 (Cat. No. T-7310 on page 118). with activity superior to that of erlotinib. Li, D. et al., “BIBW2992, AG 490 — see Tyrphostin AG 490 (Cat. No. T-9142 on page 118). an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models.” Oncogene 27: 4702‑4711 (2008). AG-013736 — see Axitinib, Free Base (Cat. No. A-1107 on page 7). • Combination treatment of HER2(YVMA) transgenic mice AGL-1872 — see PP1, Free Base (Cat. No. P-6420 on page 92). or H1781 xenografts with afatinib and rapamycin caused significant tumor shrinkage and was an effective treatment AIC-Riboside — see AICAR, Free Base (Cat. No. A-1098 on page 5). paradigm in the adenosquamous lung tumor model in mice. AICA-riboside — see AICAR, Free Base (Cat. No. A-1098 on page 5). Perera, S.A. et al., “HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy.” Proc. Natl. Acad. Sci. USA 106: 474‑479 (2009). • The EGFR T854A mutation reduces the inhibition of tyrosine phosphorylation by erlotinib. Afatinib overcomes the resistance. Bean, J. et al., “Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma.” Clin. Cancer Res. 14: 7519‑7525 (2008). • Tumors overexpressing EGFR with the secondary T790M point mutation show resistance to the first-generation EGFR inhibitors gefitinib and erlotinib. Such resistance is overcome by afatinib. Minkovsky, N. and Berezov, A., “BIBW-2992, a dual receptor

4 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

and white quadriceps. AICAR increased insulin suppressibility A-1098 AICAR, Free Base, >99% of hepatic glucose output. Thus, AICAR or similar compounds Synonyms: [Acadesine] [AIC-Riboside] may have potential in treating insulin-resistant states and type [AICA-riboside] [5-Aminoimidazole-4-carboxamide 2 diabetes. Iglesias, M.A. et al., “AICAR administration causes riboside] [GP 1-110] [Z-Riboside] an apparent enhancement of muscle and liver insulin action in Related Terms: [Arasine] [Protara] insulin-resistant high-fat-fed rats.” Diabetes 51: 2886‑2894 (2002). • AICAR was found to be a proficient cytotoxic agent in acute Size US$ ¤ £ ¥ lymphoblastic leukemia cells. The mechanisms of its anti- 25 mg 28 21 19 2,700 proliferative and apoptotic effect appeared to be through activation of p38-MAPK pathway, enhanced expression of cell 50 mg 47 36 31 4,500 cycle inhibitory proteins p27 and p53, and downstream effects 100 mg 79 60 52 7,500 on the mTOR pathway. Sengupta, T.K. et al., “Cytotoxic effect 200 mg 139 106 92 13,200 of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside 250 mg 158 121 105 15,100 (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: 500 mg 285 218 189 27,200 implication for targeted therapy.” Mol. Cancer 6: 46 (2007). 1 g 532 407 352 50,700 • NOMENCLATURE: The names “AICAR” and “Acadesine” have 2 g 994 760 658 94,700 been used by various vendors in conflicting ways, to describe NOTE: Euro, Pound and Yen prices are revised regularly. either the non-phosphorylated compound or the 5'-phosphorylated Please visit www.LCLabs.com for our current prices. compound. Our AICAR product is the non-phosphorylated compound, and we have chosen to use “AICAR” as our product M.W. 258.23 c9H14N4O5 [2627-69-2] M.I. 14: 2752 name because that name has become the more widely used of the two names for the unphosphorylated compound. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 40 mg/mL; soluble in ethanol at 2 mg/mL with • AICAR was the active ingredient in drug formulations apparently prepared for human clinical trials and referred to under the trade warming; soluble in water at 20 mg/mL with warming; ® ® buffers, serum, or other additives may increase or names Arasine and Protara . NOTE: THE AICAR, FREE BASE decrease the aqueous solubility. Disposal: A RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ARASINE® NOR PROTARA® AND IS NOT FOR HUMAN • AICAR, also known as acadesine, is an adenosine regulating agent USE. and AMPK activator. • Sold for laboratory or manufacturing purposes only; not for • Treatment with AICAR before and during coronary artery bypass human, veterinary, food, or household use. graft surgery in patients reduced early cardiac death, perioperative • This product is offered for R&D use in accordance with (i) 35 myocardial infarction, and combined adverse cardiovascular USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese outcomes. Mangano, D.T., “Effects of acadesine on myocardial Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent infarction, stroke, and death following surgery. A meta-analysis Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. of the 5 international randomized trials. The Multicenter Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Study of Perioperative Ischemia (McSPI) Research Group.” and other common law exemptions of Canadian patent law; (vi) J.A.M.A. 277: 325‑332 (1997). Section 68B of the Patents Act of 1953 in New Zealand together • Perfusion of rat hindlimbs with medium containing AICAR with the amendment of same by the Statutes Amendment Bill of was found to activate AMP-activated protein kinase (AMPK) in 2002; (vii) such related legislation and/or case law as may be or skeletal muscle, inhibit acetyl-CoA carboxylase, reduce malonyl- become applicable in the aforementioned countries; and (viii) such CoA, and increase fatty acid oxidation and glucose uptake. similar laws and rules as may apply in various other countries. Merrill, G.F. et al., “AICA riboside increases AMP-activated • Not available in some countries; not available to some institutions; protein kinase, fatty acid oxidation, and glucose uptake in rat not available for some uses. muscle.” Am. J. Physiol. 273: E1107‑E1112 (1997). • After 45 minutes of blocking of a side branch of the left coronary O H N artery in the dog, the ischemic area was reperfused for 3 hours 2 and needle biopsies were taken for biochemical analysis. Adenine N H N nucleotide de novo synthesis was shown to be very slow and it 2 HO N was doubled after ischemia. Adenine nucleotide synthesis was O improved 5-fold by ribose (the basic substrate of the adenine nucleotide de novo synthesis), 9-fold by AICAR (an intermediate OH OH of the adenine nucleotide de novo synthesis), and 90-fold by adenosine (a substrate of the nucleotide salvage pathway). Alimta — see its active ingredient, namely Pemetrexed, Mauser, M. et al., “Influence of ribose, adenosine, and “AICAR” Disodium Salt, Heptahydrate (Cat. No. P-7177 on page 84). on the rate of myocardial adenosine triphosphate synthesis Alkaban-AQ — see its active ingredient, namely Vinblastine, during reperfusion after coronary artery occlusion in the dog.” Sulfate Salt (Cat. No. V-7300 on page 121). Circ. Res. 56: 220‑230 (1985). • AICAR increased glucose uptake and the translocation of the 17-(Allylamino)-17-demethoxygeldanamycin — see 17-AAG glucose transporter likely by activating AMPK. Bergeron, R. et al., (Cat. No. A-6880 on page 1). “Effect of AMPK activation on muscle glucose metabolism in Alvespimycin — see 17-DMAG (Cat. No. D-3440 on page 28). conscious rats.” Am. J. Physiol. 276: E938‑E944 (1999). • Acute AICAR treatment inhibited hormone-sensitive lipase phosphorylation and activation, and had similar antilipolytic effects on both visceral and subcutaneous adipocytes. Anthony, N.M. et al., “Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation.” Obesity 17: 1312‑1317 (2009). • The effects of AICAR on insulin action were determined in insulin-resistant high-fat-fed rats. AICAR enhanced the glucose infusion rate during the clamp. Insulin-stimulated glucose uptake was improved by AICAR in white but not in red quadriceps, whereas glycogen synthesis was improved by AICAR in both red

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 5 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

models of rheumatoid arthritis with small-molecule cyclin- A-3465 Alvocidib, Free Base, >99% dependent kinase inhibitors.” J. Immunol. 180: 1954‑1961 (2008). Synonyms: [CPB] [DB03496] [Flavo] [Flavopiridol] • Alvocidib has potent antiviral activity in vitro against HIV-1 [HL-275] [HMR-1275] [L86-8275] [LS-39494] and HSV-1. Schang, L.M., “Effects of pharmacological cyclin- [MDL 107,826A] dependent kinase inhibitors on viral transcription and replication.” Biochim. Biophys. Acta. 1697: 197‑209 (2004). Size US$ ¤ £ ¥ • Related CAS numbers: 131740-09-5 for the hydrochloride salt. 5 mg 33 26 22 3,700 • Another CAS number previously assigned to alvocidib free base, 10 mg 58 45 38 6,500 namely 358739-39-6, has been deleted by CAS and is no longer in 25 mg 108 83 71 12,100 use. 50 mg 166 128 110 18,600 • Sold for laboratory or manufacturing purposes only; not for 100 mg 296 229 196 33,100 human, veterinary, food, or household use. 200 mg 532 411 352 59,500 • This product is offered for R&D use in accordance with (i) 35 500 mg 735 568 486 82,200 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 1 g 1090 843 721 121,900 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) M.W. 401.84 c H ClNO [146426-40-6] 21 20 5 Section 68B of the Patents Act of 1953 in New Zealand together M.I. 14: 4094 with the amendment of same by the Statutes Amendment Bill of Storage: Store at or below -20 ºC. Solubility: Soluble in 2002; (vii) such related legislation and/or case law as may be or DMSO. Disposal: A become applicable in the aforementioned countries; and (viii) such • Alvocidib, also known as flavopiridol or HMR-1275, is a cyclin- similar laws and rules as may apply in various other countries. dependent kinase (CDK) inhibitor. • Not available in some countries; not available to some institutions; • Alvocidib is a broad-spectrum inhibitor of CDKs and targets not available for some uses. their ATP binding sites. It promotes cell cycle arrest and OH O apoptosis, induces differentiation, blocks transcription elongation, and inhibits angiogenesis. Senderowicz, A.M., “Small-

molecule cyclin-dependent kinase modulators.” Oncogene HO O 22: 6609‑6620 (2003). H HO • Administration of flavopiridol to older (>70 years) chronic Cl lymphocytic leukemia patients is feasible, tolerable, and has comparable efficacy to that in younger patients (<70 years). N CH Stephens, D.M. et al., “Flavopiridol treatment of patients aged 70 3 or older with refractory or relapsed chronic lymphocytic leukemia is a feasible and active therapeutic approach.” Haematologica 97: 423‑427 (2012). AMG-706 — see Motesanib, Free Base (Cat. No. M-2900 on page 69) and Motesanib, Diphosphate Salt (Cat. No. M-2999 on page 70). • Preclinical studies have shown that alvocidib induces apoptosis in both normal and malignant cells, particularly those of 5-Aminoimidazole-4-carboxamide riboside — see hematopoietic origin. Arguello, F. et al., “Flavopiridol induces AICAR, Free Base (Cat. No. A-1098 on page 5). apoptosis of normal lymphoid cells, causes immunosuppression, 2'-Amino-3'-methoxyflavone — see PD 98059 and has potent antitumor activity in vivo against human leukemia (Cat. No. P-4313 on page 82). and lymphoma xenografts.” Blood 91: 2482‑2490 (1998). • Alvocidib potentiates paclitaxel-induced apoptosis in the human AMN-107 — see Nilotinib (Cat. No. N-8207 on page 72). gastric and breast cancer cell lines MKN‑74 and MCF‑7. AMPK Inhibitor I — see Dorsomorphin, Free Base Motwani, M. et al., “Sequential dependent enhancement of (Cat. No. D‑3197 on page 30) and Dorsomorphin, caspase activation and apoptosis by flavopiridol on paclitaxel- Dihydrochloride Salt (Cat. No. D‑3456 on page 31). treated human gastric and breast cancer cells.” Clin. Cancer Res. 5: 1876‑1883 (1999). Anthra(1,9-cd)pyrazol-6(2H)-one — see SP600125 (Cat. No. S-7979 on page 107). • Alvocidib (100-200 nM) potentiates phorbol 12-myristate 13-acetate (PMA, 10 nM)-induced apoptosis in human myeloid Anthrapyrazolone — see SP600125 (Cat. No. S-7979 on page 107). leukemia cells U937 and HL-60. Cartee, L. et al., “Synergistic induction of apoptosis in human myeloid leukemia cells by Antibiotic AM-2282 — see Staurosporine phorbol 12-myristate 13-acetate and flavopiridol proceeds (Cat. No. S‑9300 on page 108). via activation of both the intrinsic and tumor necrosis factor- Antibiotic S 7481F1 — see Cyclosporin A mediated extrinsic cell death pathways.” Mol. Pharmacol. (Cat. No. C‑6000 on page 25). 61: 1313‑1321 (2002). AP 23573 — see Ridaforolimus (Cat. No. R-7040 on page 97). • In early clinical trials, alvocidib demonstrated limited activity in patients with gastric carcinoma and lung cancer. Schwartz, G.K. AP 24534 — see Ponatinib, Free Base (Cat. No. P-7022 on page 92). et al., “Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Arasine — see its active ingredient, namely AICAR, Free Base Carcinoma.” J. Clin. Oncol. 19: 1985‑1992 (2001). Shapiro, G.I. (Cat. No. A-1098 on page 5). et al., “A Phase II Trial of the Cyclin-dependent Kinase Inhibitor Armala — see its active ingredient, namely Pazopanib, Free Base Flavopiridol in Patients with Previously Untreated Stage IV Non- (Cat. No. P-6706 on page 81). Small Cell Lung Cancer.” Clin. Cancer Res. 7: 1590‑1599 (2001). ARRY-886 — see Selumetinib, Free Base • In vitro, alvocidib inhibited proliferation of human and mouse (Cat. No. S-4490 on page 104). synovial fibroblasts. In vivo, treatment with alvocidib suppressed synovial hyperplasia and joint destruction in mice with collagen- ARRY-142886 — see Selumetinib, Free Base induced arthritis. Sekine, C. et al., “Successful treatment of animal (Cat. No. S-4490 on page 104).

6 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

A-1040 Ascomycin, >99% Ascotoxin — see Brefeldin A (Cat. No. B-8500 on page 14). [FK-520] [FR-900520] [Immunomycin] [L 683590] AT-877 – see Fasudil, Monohydrochloride Salt (Cat. No. F-4660 on page 40) and HA-1077 (Cat. No. H-2330 on page 52). Size US$ ¤ £ ¥ 25 mg 53 41 35 5,900 ATM Kinase Inhibitor — see KU-55933 (Cat. No. K-5050 on page 62). 100 mg 78 60 52 8,700 AUY922 — see NVP-AUY922, Free Base 250 mg 122 94 81 13,600 (Cat. No. N-5300 on page 74). 1 g 415 321 274 46,400 AV-951 — see Tivozanib, Free Base (Cat. No. T-6466 on page 113). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. A-1107 Axitinib, Free Base, >99%

M.W. 792.01 C43H69NO12 [104987-12-4] Synonyms: [AG-013736] Storage: Store at or below -20 ºC. Solubility: Soluble in Related Terms: [Inlyta] DMSO at 65 mg/mL; soluble in ethanol at 50 mg/mL after warming; very poorly soluble in water; maximum solubility Size US$ ¤ £ ¥ in plain water is estimated to be about 10-50 µM; buffers, 50 mg 44 34 29 4,900 serum, or other additives may increase or decrease the 100 mg 76 59 50 8,500 aqueous solubility. Disposal: A 200 mg 127 98 84 14,200 • Ascomycin (also known as Immunomycin, FR 900520, 500 mg 288 223 190 32,200 and FK-520) is an analog of tacrolimus (FK-506) with 1 g 461 356 305 51,500 immunosuppressive, neurotrophic and antifungal activities. Ascomycin can be used to prevent rejection after an organ 2 g 870 673 575 97,300 transplant, and to treat autoimmune diseases and skin diseases. 5 g 1960 1515 1296 219,100 NOTE: Euro, Pound and Yen prices are revised regularly. • Ascomycin inhibits the production of T helper type 1 (Th1) Please visit www.LCLabs.com for our current prices. (interferon and IL-2) and Th2 (IL-4 and IL-10) cytokines in target cells. Paul, C. et al., “Ascomycins: promising M.W. 386.47 C22H18N4OS [319460-85-0] agents for the treatment of inflammatory skin diseases.” M.I. 14: 10304 Expert Opin. Investig. Drugs 9: 69‑77 (2000). Mollison, K.W. Storage: Store at or below -20 ºC. Solubility: Soluble in et al., “A macrolactam inhibitor of T helper type 1 and T helper DMSO at 33 mg/mL; soluble in ethanol at 1.7 mg/mL with type 2 cytokine biosynthesis for topical treatment of inflammatory warming; very poorly soluble in water; maximum solubility skin diseases.” J. Invest. Dermatol. 112: 729‑738 (1999). in plain water is estimated to be about 10-50 µM; buffers, • Antimalarial effects of ascomycin appear to be independent of its serum, or other additives may increase or decrease the immunosuppressive properties. Monaghan, P. et al., “Antimalarial aqueous solubility. Disposal: A effects of macrolactones related to FK520 (ascomycin) are • Axitinib (AG-013736) is an oral, potent, and selective inhibitor independent of the immunosuppressive properties of the of vascular endothelial growth factor receptors 1 (VEGFR-1), 2 compounds.” J. Infect. Dis. 191: 1342‑1349 (2005). (VEGFR-2), and 3 (VEGFR-3), platelet derived growth factor • FK-520 might be a substrate for P-glycoprotein; expression of receptor (PDGFR), and cKIT (CD117). P-glycoprotein in yeast cells resulted in resistance to growth • Axitinib inhibited growth of breast tumors in vivo at doses of 10- inhibition by FK-520. Raymond, M. et al., “Functional expression 100 mg/kg and disrupted tumor microvasculature as measured by of P-glycoprotein in Saccharomyces cerevisiae confers cellular dynamic contrast-enhanced MRI. Wilmes, L.J. et al., “AG-013736, resistance to the immunosuppressive and antifungal agent FK520.” a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast Mol. Cell Biol. 14: 277‑286 (1994). cancer growth and decreases vascular permeability as detected • We note that one of our competitors, AG Scientific, as of by dynamic contrast-enhanced magnetic resonance imaging.” February 3, 2014, is claiming 99.9% purity for its Ascomycin. Magn. Reson. Imaging. 25: 319‑327 (2007). This claim is not credible in general chemical terms for this • Regrowth of blood vessels in spontaneous RIP-Tag2 tumors complex organic compound, nor in terms of the sensitivity and and implanted Lewis lung carcinomas in mice was studied after reproducibility of generally utilized analytical techniques. being treated with axitinib or AG-028262 for 7 days. Both agents • Sold for laboratory or manufacturing purposes only; not for inhibited 50%-60% of tumor neovasculature formation. Empty human, medical, veterinary, food, or household use. sleeves of basement membrane were left behind and surviving • Please see also our other standard immunosuppressant products: pericytes had less α-SMA immunoreactivity. Endothelial sprouts - Cyclosporin A (Cat. No. C-6000 on page 25). grew into empty sleeves of basement membrane one day after drug withdrawal, which was followed by vessel patency and connection - Everolimus (Cat. No. E-4040 on page 40). to the bloodstream. Tumors were fully revascularized and the - FK-506 (Cat. No. F-4900 on page 42). pericyte phenotype returned to baseline by 7 days. Mancuso, M.R. - Pimecrolimus (Cat. No. P-6040 on page 91). et al., “Rapid vascular regrowth in tumors after reversal of VEGF - Rapamycin (Cat. No. R-5000 on page 96). inhibition.” J. Clin. Invest. 116: 2610‑2621 (2006). - Temsirolimus (Cat. No. T-8040 on page 111). • Axitinib inhibited angiogenesis significantly in rat 9L tumors grown s.c. in scid mice but only delayed tumor growth moderately. - Zotarolimus, Free Base (Cat. No. Z-9040 on page 128). A combination of axitinib with metronomic cyclophosphamide HO completely blocked 9L tumor growth on initiation of drug treatment. However, metronomic cyclophosphamide alone required multiple treatment cycles to inhibit tumor growth. H CO CH 3 3 Ma, J. and Waxman, D.J., “Modulation of the antitumor activity H C O 3 of metronomic cyclophosphamide by the angiogenesis inhibitor O OH CH axitinib.” Mol. Cancer Ther. 7: 79‑89 (2008). 3 N • Axitinib has clinical activity in patients with cytokine-refractory O metastatic renal-cell cancer. Rixe, O. et al., “Axitinib treatment in O CH O 3 OH patients with cytokine-refractory metastatic renal-cell cancer: a H C CH 3 O 3 phase II study.” Lancet Oncol. 8: 975‑984 (2007).

OCH OCH 3 3

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 7 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Axitinib is the active ingredient in the drug sold under the trade respectively. In cells, it inhibited autophosphorylation of FGFR1, ® name Inlyta . This drug is currently approved in at least one 2, and 3 tyrosine kinases with IC50 values of 12, 2, and 40 nM, country for the treatment of advanced renal cell carcinoma. NOTE: respectively. It had potent antitumor activity against FGFR- THE AXITINIB, FREE BASE RESEARCH COMPOUND deregulated tumors in preclinical models. Gavine, P.R. et al., SOLD BY LC LABORATORIES IS NOT INLYTA® AND IS "AZD4547: an orally bioavailable, potent, and selective inhibitor NOT FOR HUMAN USE. Inlyta® is a registered trademark of the fibroblast growth factor receptor tyrosine kinase family." of Pfizer Corporation. LC Laboratories is not affiliated with Cancer Res. 72: 2045‑2056 (2012). Pfizer Corporation, and the axitinib research compound sold by • AZD4547 inhibited the growth of gastric cancer cell lines LC Laboratories is not manufactured by Pfizer Corporation. SNU-16 and KATO-III, carrying the amplified FGFR2 gene, • Sold for laboratory or manufacturing purposes only; not for with GI50 values of 3 and 5 nM, respectively. It also effectively human, medical, veterinary, food, or household use. inhibited phosphorylation of FGFR2 and its downstream signaling • This product is offered for R&D use in accordance with (i) 35 molecules and resulted in apoptosis in SNU-16 cells. Furthermore, USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese it significantly inhibited the tumor growth in FGFR2-amplified Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent xenograft (SNU-16) and PDGCX models (SGC083) but not in Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. nonamplified models. Xie, L. et al., "FGFR2 gene amplification in Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) gastric cancer predicts sensitivity to the selective FGFR inhibitor and other common law exemptions of Canadian patent law; (vi) AZD4547." Clin. Cancer Res. 19: 2572‑2583 (2013). Section 68B of the Patents Act of 1953 in New Zealand together • AZD4547 inhibited the cell growth only in those lines harboring with the amendment of same by the Statutes Amendment Bill of amplified FGFR1 with GI50 values of 3-111 nM. AZD4547 caused 2002; (vii) such related legislation and/or case law as may be or tumor stasis or regressive effects in four of five FGFR1-amplified become applicable in the aforementioned countries; and (viii) such squamous non-small cell lung cancer patient-derived tumor similar laws and rules as may apply in various other countries. xenograft models. Zhang, J. et al., "Translating the therapeutic • Not available in some countries; not available to some institutions; potential of AZD4547 in FGFR1-amplified non-small cell not available for some uses. lung cancer through the use of patient-derived tumor xenograft models." Clin. Cancer Res. 18: 6658‑6667 (2012).

NH O • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. S NH • This product is offered for R&D use in accordance with (i) 35 N USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6)

N and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of AY-22989 — see Rapamycin (Cat. No. R-5000 on page 96). 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such 5-Aza-dC — see Decitabine, Free Base (Cat. No. D‑3899 on page 27). similar laws and rules as may apply in various other countries. 5-Aza-2'-deoxycytidine — see Decitabine, Free Base • Not available in some countries; not available to some institutions; (Cat. No. D‑3899 on page 27). not available for some uses.

O O Azaepothilone B — see Ixabepilone, Free Base H C CH 3 3 (Cat. No. I-5022 on page 58). H N CH N H 3 AZD 0530 — see Saracatinib, Free Base N (Cat. No. S-8906 on page 102). N NH AZD-2281 — see Olaparib (Cat. No. O-9201 on page 78). O CH 3 AZD2171 — see Cediranib, Free Base (Cat. No. C-4300 on page 19). AZD6244 — see Selumetinib, Free Base A-1088 AZD4547, Free Base, >99% (Cat. No. S-4490 on page 104). Size US$ ¤ £ ¥ A-2345 AZD8055, Free Base, >99% 5 mg 42 30 25 4,800 Synonyms: [CCG-168] New! 10 mg 51 37 31 5,800 25 mg 84 60 50 9,500 Size US$ ¤ £ ¥ 50 mg 114 82 68 13,000 5 mg 37 27 22 4,200 100 mg 178 128 107 20,200 New! 10 mg 49 35 29 5,600 200 mg 272 196 163 30,900 25 mg 85 61 51 9,700 NOTE: Euro, Pound and Yen prices are revised regularly. 50 mg 115 83 69 13,100 Please visit www.LCLabs.com for our current prices. 100 mg 184 132 111 20,900 M.W. 463.57 C26H33N5O3 [1035270-39-3] 200 mg 332 239 199 37,700 Storage: Store at or below -20 ºC. Solubility: Soluble in NOTE: Euro, Pound and Yen prices are revised regularly. DMSO at 90 mg/mL; soluble in ethanol at 25 mg/mL with Please visit www.LCLabs.com for our current prices. warming; very poorly soluble in water; maximum solubility M.W. 465.54 c25H31N5O4 [1009298-09-2] in plain water is estimated to be about 25-50 µM; buffers, Storage: Store at or below -20 ºC. Solubility: Soluble in serum, or other additives may increase or decrease the DMSO at 50 mg/mL; soluble in ethanol at 20 mg/mL with aqueous solubility. Disposal: A warming; very poorly soluble in water; maximum solubility • AZD4547 is a novel and selective inhibitor of the fibroblast in plain water is estimated to be about 50-100 µM; buffers, growth factor receptor (FGFR) 1, 2, and 3 tyrosine kinases. It serum, or other additives may increase or decrease the potently inhibited the tyrosine kinase activities of recombinant aqueous solubility. Disposal: A FGFR1, 2, and 3 in vitro with IC50 values of 0.2, 2.5, and 1.8 nM,

8 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• AZD8055 is a novel ATP-competitive and selective inhibitor of • Sold for laboratory or manufacturing purposes only; not for mammalian target of rapamycin (mTOR) kinase with an IC50 value human, veterinary, food, or household use. of 0.8 nM. It inhibits the phosphorylation of mTORC1 substrates • This product is offered for R&D use in accordance with (i) 35 p70S6K and 4E-BP1, mTORC2 substrate AKT, and downstream USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese proteins. AZD8055 fully inhibits the rapamycin-resistant T37/46 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent phosphorylation sites on 4E-BP1 and results in significant Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. inhibition of cap-dependent translation. AZD8055 potently inhibits Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) proliferation and induces autophagy in vitro, and causes significant and other common law exemptions of Canadian patent law; (vi) growth inhibition and/or regression in xenografts in vivo. Section 68B of the Patents Act of 1953 in New Zealand together Chresta, C.M. et al., "AZD8055 is a potent, selective, and orally with the amendment of same by the Statutes Amendment Bill of bioavailable ATP-competitive mammalian target of rapamycin 2002; (vii) such related legislation and/or case law as may be or kinase inhibitor with in vitro and in vivo antitumor activity." become applicable in the aforementioned countries; and (viii) such Cancer Res. 70: 288‑298 (2010). similar laws and rules as may apply in various other countries. • The combination of the MAPK extracellular signal-regulated • Not available in some countries; not available to some institutions; kinase (MEK1/2) inhibitor selumetinib (AZD6244, please see not available for some uses. Selumetinib, Free Base, Cat. No. S-4490 on page 104) with the dual mTORC1 and mTORC2 inhibitor AZD8055 were used in nude O mouse xenograft models of human lung adenocarcinoma (non- N CH small cell lung cancers) and colorectal carcinoma. The treatment 3 was well tolerated and showed improved antitumor efficacy when compared to the respective monotherapies. The reciprocal pathway OH N inhibition from the combination group was associated with increased apoptosis and Bcl-2 interacting mediator of cell death N N N H C O 3 (Bim) expression in tumor tissue. Holt, S.V. et al., "Enhanced O H C apoptosis and tumor growth suppression elicited by combination 3 of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055)." B705008K112 — see Bryostatin 1 (Cat. No. B-6697 on page 15). Cancer Res. 72: 1804‑1813 (2012). • The mTOR molecular signaling pathway plays a critical role in B-1080 Bafilomycin A1, >98% cerebral vasospasm following subarachnoid hemorrhage (SAH). AZD8055 significantly inhibited the level and expression of Size US$ ¤ £ ¥ key mTOR signaling pathway molecules including mTOR, 1 mg 59 44 37 5,800 P70S6K1, 4E-BP1 and PCNA, and thus inhibited the mTOR Prices 5 mg 198 148 124 19,600 pathway, thus suggesting that AZD8055 has the potential to treat Reduced! 10 mg 313 234 195 31,000 vasospasm following SAH. Zhang, W. et al., "Mammalian target 25 mg 588 440 367 58,300 of rapamycin (mTOR) inhibition reduces cerebral vasospasm NOTE: Euro, Pound and Yen prices are revised regularly. following a subarachnoid hemorrhage injury in canines." Please visit www.LCLabs.com for our current prices. Exp. Neurol. 233: 799‑806 (2012). M.W. 622.83 c H O [88899-55-2] • AZD8055 inhibited both mTORC1 and mTORC2 signaling in 35 58 9 acute myeloid leukemia (AML) in mice. AZD8055 significantly Storage: Store at or below -20 °C. Solubility: Soluble reduced the tumor growth and markedly increased the in DMSO at 200 mg/mL; may react with methanol or survival of AML transplanted mice without apparent toxicity. ethanol, so these solvents are not recommended for stock Willems, L. et al., "The dual mTORC1 and mTORC2 inhibitor solutions; very poorly soluble in water; maximum solubility AZD8055 has anti-tumor activity in acute myeloid leukemia." in plain water is estimated to be about 5-10 µM; buffers, Leukemia 26: 1195‑1202 (2012). serum, or other additives may increase or decrease the aqueous solubility. Appearance: Clear film. Disposal: A • AZD8055 blocked the chemotherapy-induced cell death promoted by ectopic wild-type p62. Huang, S. et al., "Inhibition of mTOR • Specific, potent inhibitor of vacuolar ATPases. Bowman, E. kinase by AZD8055 can antagonize chemotherapy-induced cell et al., “Bafilomycins: A class of inhibitors of membrane death through autophagy induction and down-regulation of p62/ ATPase from microorganisms, animal cells, and plant cells.” sequestosome 1." J. Biol. Chem. 286: 40002‑40012 (2011). Proc. Natl. Acad. Sci. USA 85: 7972‑7976 (1988). • The combination of mTOR kinase inhibitor AZD8055 and • Sold for laboratory or manufacturing purposes only; not for histone deacetylase inhibitor SAHA (please see Vorinostat, human, medical, veterinary, food, or household use. Cat. No. V-8477 on page 124) almost completely inhibited tumor OCH3 CH3 CH3 growth of hepatocellular carcinoma (HCC) by upregulating Bim OH O OH and abrogating AKT. However, either agent alone demonstrated H C 3 CH only 30% inhibition in primary HCC xenografts. Shao, H. et al., OH O 3 "Dual targeting of mTORC1/C2 complexes enhances histone H C 3 O deacetylase inhibitor-mediated anti-tumor efficacy in primary OH H HCC cancer in vitro and in vivo." J. Hepatol. 56: 176‑183 (2012). CH3 CH3 CH3 OCH3 CH3 • Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumors were tested in Western Bay 43-9006 — see Sorafenib, Free Base (Cat. No. S-8599 patients and Japanese patients. The maximum tolerated dose for on page 105) and Sorafenib, p-Toluenesulfonate Salt AZD8055 was 90 mg BID. Aside from elevated transaminases, (Cat. No. S-8502 on page 106). the drug had an acceptable toxicity profile. Naing, A. et al., 4'-N-Benzoyl Staurosporine — see PKC412 "Safety, tolerability, pharmacokinetics and pharmacodynamics (Cat. No. P-7600 on page 91). of AZD8055 in advanced solid tumours and lymphoma." Br. J. Cancer 107: 1093‑1099 (2012). Asahina, H. et al., N-Benzoyl-7-oxostaurosporine — see Stauprimide "Safety and tolerability of AZD8055 in Japanese patients (Cat. No. S-9344 on page 108). with advanced solid tumors; a dose-finding phase I study." Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone — see Invest. New Drugs 31: 677‑684 (2013). Z-VAD-FMK, Methyl Ester (Cat. No. Z-9900 on page 127). • Related CAS numbers: 1201799-05-4 for the fumarate salt form of Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone — see AZD8055. Z-VAD-FMK, Free Acid (Cat. No. Z-9999 on page 127).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 9 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

treatment of patients with CTCL. NOTE: the bexarotene sold by B-2422 Bexarotene, Free Acid, >99% LC Laboratories is NOT Targretin® and is NOT for human use. [LG 1069] [LGD-1069] [LG100069] [SR-11247] • Sold for laboratory or manufacturing purposes only; not for [Targretin] [Targretyn] [Targrexin] human, medical, veterinary, food, or household use. Size US$ ¤ £ ¥ • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 100 mg 57 44 38 6,400 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 300 mg 87 67 58 9,700 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 500 mg 107 83 71 12,000 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 1 g 176 136 116 19,700 and other common law exemptions of Canadian patent law; (vi) 2 g 318 246 210 35,600 Section 68B of the Patents Act of 1953 in New Zealand together 5 g 745 576 493 83,300 with the amendment of same by the Statutes Amendment Bill of 10 g 1170 904 773 130,800 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; M.W. 348.48 c24H28O2 [153559-49-0] M.I. 14: 1194 not available for some uses. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 65 mg/mL; soluble in ethanol at 10 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A • Bexarotene (LGD-1069) is a synthetic retinoid analog with

specific affinity for the retinoid X receptor and belongs to a group O OH of compounds called rexinoids. It is an oral, noncytotoxic drug that was approved in Europe and in the U.S.A. for the treatment of BEZ235 — see NVP-BEZ235, Free Base refractory advanced-stage cutaneous T-cell lymphomas (CTCL). (Cat. No. N‑4288 on page 75). Gniadecki, R. et al., “The optimal use of bexarotene in cutaneous T-cell lymphoma.” Br. J. Dermatol. 157: 433‑440 (2007). BFA — see Brefeldin A (Cat. No. B-8500 on page 14). • A mouse model of Alzheimer’s disease was treated with oral BIBF1120 — see Nintedanib, Free Base (Cat. No. N-9077 on page 72). administration of bexarotene, a retinoid X receptor agonist. Bexarotene treatment significantly enhanced the clearance BIBF1120 Esylate — see Nintedanib, Ethanesulfonate Salt of soluble β-amyloid (Aβ) from the brain within hours in an (Cat. No. N-9055 on page 73). apolipoprotein E-dependent manner. It reduced Aβ plaque area BIBW-2992 — see Afatinib, Free Base (Cat. No. A-8644 on page 4). more than 50% within just 72 hours. Bexarotene treatment also resulted in the rapid reversal of cognitive, social, and olfactory B-7100 BIIB021, Free Base, >99% deficits and improved neural circuit function. Cramer, P.E. et al., Synonyms: [CNF2024] “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.” Science 335: 1503-1506 (2012). Size US$ ¤ £ ¥ • Compared with historical results with combination 5 mg 52 38 31 6,300 chemotherapy alone, bexarotene in combination with Prices 10 mg 81 60 48 9,800 chemotherapeutic agents has showed an encouraging median Reduced! 25 mg 145 107 85 17,500 survival for patients with advanced non-small cell lung cancer. Rigas, J.R. and Dragnev, K.H., “Emerging Role of Rexinoids 50 mg 215 158 126 26,000 in Non-Small Cell Lung Cancer: Focus on Bexarotene.” 100 mg 328 241 193 39,600 The Oncologist 10: 22‑33 (2005). 200 mg 532 391 313 64,300 • The receptor-selective retinoids might be particularly useful in 250 mg 615 452 361 74,300 preventing ER-negative breast cancer. Wu, K. et al., “The retinoid 500 mg 845 621 497 102,100 X receptor-selective retinoid, LGD1069, prevents the development 1 g 1170 860 688 141,300 of estrogen receptor-negative mammary tumors in transgenic NOTE: Euro, Pound and Yen prices are revised regularly. mice.” Cancer Res. 62: 6376‑6380 (2002). Please visit www.LCLabs.com for our current prices.

• Results from cell culture treatments and in vivo xenograft M.W. 318.76 C14H15ClN6O [848695-25-0] models suggested that bexarotene in combination with Storage: Store at or below -20 ºC. Solubility: Soluble in chemotherapeutic agents might play an important role in DMSO at 65 mg/mL; soluble in ethanol at 3 mg/mL with preventing and overcoming acquired drug resistance in advanced warming; very poorly soluble in water; maximum solubility prostate cancer, breast carcinoma, and non-small cell lung in plain water is estimated to be about 50‑100 µM; buffers, cancer. Yen, W.C. and Lamph, W.W., “A selective retinoid X serum, or other additives may increase or decrease the receptor agonist bexarotene (LGD1069, Targretin) prevents and aqueous solubility. Disposal: A overcomes multidrug resistance in advanced prostate cancer.” Prostate 66: 305‑316 (2006). Yen, W.C. and Lamph, W.W., “The • BIIB021 is an orally available, synthetic small-molecule selective retinoid X receptor agonist bexarotene (LGD1069, Hsp90 inhibitor. It binds in the ATP-binding pocket of Hsp90 Targretin) prevents and overcomes multidrug resistance in (Ki = 1.7 ± 0.4 nM) and induces HER-2 degradation with an advanced breast carcinoma.” Mol. Cancer Ther. 4: 824‑834 (2005). EC50 of 38 ± 10 nM in MCF-7 cells. It induces the degradation Yen, W.C. et al., “A selective retinoid X receptor agonist of client proteins (HER2, pHER2, IGFR-1R, AKT, pAKT, Raf1, bexarotene (Targretin) prevents and overcomes acquired paclitaxel pRaf, Cdk4, Cdk6, cyclinD, ER, and PR), increases expression (Taxol) resistance in human non-small cell lung cancer.” of the heat shock proteins Hsp90a and Hsp70, but has no effect Clin. Cancer Res. 10: 8656‑8664 (2004). on expression of the nonclient protein phosphatidylinositol 3-kinase p85 subunit. BIIB021 inhibits the proliferation of N87, • Bexarotene is the active ingredient in the drug sold under the trade ® MCF-7, and BT474 tumor cells with IC50 values of 0.06, 0.31, name Targretin . The drug is approved in at least one country for and 0.14 µM, respectively. It has significant antitumor activity in

10 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

N87 stomach, BT474 breast, CWR22 prostate, U87 glioblastoma, BMP Inhibitor I — see Dorsomorphin, Free Base SKOV3 ovarian, and Panc-1 pancreatic tumor xenograft models. (Cat. No. D‑3197 on page 30) and Dorsomorphin, Lundgren K. et al., “BIIB021, an orally available, fully synthetic Dihydrochloride Salt (Cat. No. D‑3456 on page 31). small-molecule inhibitor of the heat shock protein Hsp90.” Mol. Cancer Ther. 8: 921‑929 (2009). BMS 247550-1 — see Ixabepilone, Free Base • A Phase I clinical trail demonstrated that BIIB021 was generally (Cat. No. I-5022 on page 58). well tolerated in patients with advanced solid tumors or chronic BMS-247550 — see Ixabepilone, Free Base lymphocytic leukemia. The maximum tolerated dose of BIIB021 (Cat. No. I-5022 on page 58). was less than 800 mg twice a week. Serum and intracellular Hsp70 was increased and the serum level of Her-2/neu extracellular BMS-354825 — see Dasatinib (Cat. No. D-3307 on page 27). domain was decreased after administration. The half-life of BMY-40481 — see Etoposide (Cat. No. E-4488 on page 38) BIIB021 was about 1 hr. Elfiky A. et al., “BIIB021, an oral, and Etoposide 4'-Phosphate, Free Acid synthetic non-ansamycin Hsp90 inhibitor: Phase I experience.” (Cat. No. E-4444 on page 39). J. Clin. Oncol. 26: 2503 (2008). • BIIB021 enhanced radiosensitivity of head and neck squamous B-1408 Bortezomib, Free Base, 99% cell carcinoma (HNSCCA) in vitro and improved the efficacy of [MG-341] [PS-341] [Velcade] radiation in vivo, indicating BIIB021 may be used in HNSCCA patients as a radiosensitizer. Yin X. et al., “BIIB021, a novel Size US$ ¤ £ ¥ Hsp90 inhibitor, sensitizes head and neck squamous cell 5 mg 30 22 18 3,600 carcinoma to radiotherapy.” Int. J. Cancer. 126: 1216‑1225 (2010). Prices 10 mg 53 39 31 6,400 • BIIB021 inhibited the proliferation of P-gp and/or MRP-1 Reduced! 25 mg 114 84 67 13,800 expressing cancer cell lines. The cytotoxic activity of BIIB021 50 mg 161 118 95 19,400 was also not influenced by loss of NQO1 or Bcl-2 overexpression. 100 mg 278 204 163 33,600 Compared to 17-AAG, BIIB021 has broader applications 200 mg 432 318 254 52,200 against tumors with acquired multidrug resistance. Zhang H. et al., “BIIB021, a synthetic Hsp90 inhibitor, has broad 250 mg 515 379 303 62,200 application against tumors with acquired multidrug resistance.” 500 mg 722 531 424 87,200 Int. J. Cancer. 126: 1226‑1234 (2010). 1 g 945 695 555 114,200 • BIIB021 has antitumor activity in Hodgkin’s lymphoma in 2 g 1720 1265 1011 207,800 vitro and in vivo. BIIB021 selectively induced Hodgkin’s NOTE: Euro, Pound and Yen prices are revised regularly. lymphoma cell death but did not kill normal lymphocytes from Please visit www.LCLabs.com for our current prices. healthy individuals. BIIB021 inhibited the activity of NF-κB, M.W. 384.24 c19H25BN4O4 [179324-69-7] which was independent of IκB mutations. BIIB021 sensitized Storage: Store at or below -20 °C. Solubility: Soluble in Hodgkin’s lymphoma cells to NK cell-mediated killing, possibly DMSO at 200 mg/mL; soluble in ethanol at 200 mg/mL; by increasing the expression of some ligands engaging activating very poorly soluble in water; maximum solubility in plain NK cell receptors. Böll B. et al., “Heat shock protein 90 inhibitor water is estimated to be about 5-10 µM; buffers, serum, BIIB021 (CNF2024) depletes NF-κB and sensitizes Hodgkin’s or other additives may increase or decrease the aqueous lymphoma cells for natural killer cell-mediated cytotoxicity.” solubility. Disposal: A Clin. Cancer Res. 15: 5108‑5116 (2009). • Bortezomib, Free Base is a potent (Ki, 0.6 nM), specific and • Our BIIB021 product is the free base whose CAS number is given reversible proteasome inhibitor; it shows no significant inhibitory above. The CAS number of the hydrochloride salt is 848696-06-0. activity against other related or unrelated enzymes or receptors. • Sold for laboratory or manufacturing purposes only; not for Bouchard, PR. et al., “Nonclinical Discovery and Development human, veterinary, food, or household use. of Bortezomib (PS-341, Velcade®), a Proteasome Inhibitor for • This product is offered for R&D use in accordance with (i) 35 the Treatment of Cancer.” 55th Annual Meeting of the American USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese College of Veterinary Pathologists (ACVP) & 39th Annual Meeting Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent of the American Society of Clinical Pathology (ASVCP), ACVP Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. and ASVCP (Eds.). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • In a study with the National Cancer Institute’s panel of 60 human and other common law exemptions of Canadian patent law; (vi) cell lines, Bortezomib, Free Base displayed a mean IC50 of 7 nM Section 68B of the Patents Act of 1953 in New Zealand together as determined by SRB analysis. Adams, J. et al., “Proteasome with the amendment of same by the Statutes Amendment Bill of inhibitors: a novel class of potent and effective antitumor agents.” 2002; (vii) such related legislation and/or case law as may be or Cancer Res. 59: 2615‑2622 (1999). become applicable in the aforementioned countries; and (viii) such • Bortezomib, Free Base is active in preclinical models of human similar laws and rules as may apply in various other countries. prostate cancer, but its effects on apoptosis versus angiogenesis are • Not available in some countries; not available to some institutions; cell type dependent. Bortezomib, Free Base caused comparable, not available for some uses. concentration-dependent growth suppression in LNCaP-Pro5 Cl and PC3M-Pro4 cells (IC90 = 10 nM). Williams, S. et al., “Differential effects of the proteasome inhibitor bortezomib on N N apoptosis and angiogenesis in human prostate tumor xenografts.” Mol. Cancer Ther. 2: 835‑843 (2003). H N N N 2 N • Bortezomib, Free Base inhibits cell proliferation of H460 cells (Human non-small cell lung cancer cell lines) with an CH 3 IC50 of 0.1 µM. Ling, Y. et al., “Mechanisms of Proteasome H C 3 OCH Inhibitor PS-341-induced G2-M-Phase Arrest and Apoptosis 3 in Human Non-Small Cell Lung Cancer Cell Lines.” BIRB 796 — see Doramapimod (Cat. No. D-2744 on page 29). Clin. Cancer Res. 9: 1145‑1154 (2003). • Bortezomib, Free Base is the active ingredient in the drug sold BML-275 — see Dorsomorphin, Free Base ® (Cat. No. D‑3197 on page 30) and Dorsomorphin, under the trade name Velcade . The drug has been approved Dihydrochloride Salt (Cat. No. D‑3456 on page 31). in at least one country to treat multiple myeloma. NOTE: the bortezomib, free base sold by LC Laboratories is NOT Velcade® and is NOT for human use.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 11 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. B-1788 Bosutinib, Free Base, >99% • This product is offered for R&D use in accordance with (i) 35 Synonyms: [SKI-606] USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Related Terms: [Bosulif] Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent (LCL-XP™: LC Labs X-ray Proven Structure™) Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Size US$ ¤ £ ¥ and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together 25 mg 34 25 22 3,300 with the amendment of same by the Statutes Amendment Bill of 50 mg 47 35 30 4,500 2002; (vii) such related legislation and/or case law as may be or 100 mg 69 52 44 6,600 become applicable in the aforementioned countries; and (viii) such 200 mg 99 74 64 9,500 similar laws and rules as may apply in various other countries. 500 mg 232 174 150 22,300 • Not available in some countries; not available to some institutions; 1 g 428 321 276 41,200 not available for some uses. 2 g 784 588 506 75,500 5 g 1690 1267 1090 162,600 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. O OH

N NH B M.W. 530.45 c26H29Cl2N5O3 [380843-75-4] NH OH M.I. 14: 10347 O N Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 200 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility Bosulif – see its active ingredient, namely Bosutinib, Free Base in plain water is estimated to be about 10-50 µM; buffers, (Cat. No. B-1788 on page 12). serum, or other additives may increase or decrease the aqueous solubility. Disposal: A B-1709 Bosutinib Problem Explanation • PLEASE NOTE: our firm DID NOT synthesize the incorrect bosutinib isomer that has been widely sold in the research • Bosutinib (SKI-606) is a tyrosine kinase inhibitor, more potent reagents marketplace, and we are NOT the cause of the than imatinib. It has reached Phase II clinical trials in humans as overall bosutinib problem. Please visit www.pkcpharma. an anti-cancer agent. com/TwoOrMoreBosutinibs.html for extensive information • Aside from the ongoing clinical studies, bosutinib is also used about this problem. For a short synopsis of changes in LC extensively in biomedical research laboratories around the world, Laboratories’ products, product name, and catalog numbers, for non-human, non-veterinary studies. please visit www.lclabs.com/PRODFILE/A-C/B-1709.php4. • Very unfortunately, an incorrect isomer of bosutinib has been • X-ray, NMR and melting point data that our firm has obtained sold to laboratory researchers under the name “Bosutinib” by indicate that the following 17 vendors have erroneously 17 vendors, for various periods as long as several years. For sold, to one or more normal customers in the biochemical extensive information about this bosutinib problem, please reagent marketplace, an incorrect bosutinib isomer under visit www.pkcpharma.com/TwoOrMoreBosutinibs.html. the name “bosutinib” (please visit www.pkcpharma.com/ • LC Laboratories is one of the 17 vendors that sold the incorrect TwoOrMoreBosutinibs.html for extensive additional bosutinib isomer under the name “Bosutinib”, and the information about this problem): corresponding catalog number was B-1709. - AK Scientific • To avoid confusion, we have permanently discontinued use of - Alfa Aesar the B-1709 catalog number. All of the incorrect bosutinb isomer - Axon Medchem sold by LC Labs at any time was sold under the catalog number - B-Bridge International “B‑1709” and the name “Bosutinib, Free Base”. - Biorbyt Ltd. • We have now produced our own correct bosutinib and unambiguously proven its structure by X-ray crystallography. - Biovision Inc. We have assigned a new catalog number to this correct bosutinib - Eton Bioscience product (Bosutinib, Free Base, Cat. No. B-1788 on page 12). Please - LC Laboratories (part of PKC Pharma) see that product page for extensive information, sizes and prices. - LKT Laboratories • We now refer to the particular incorrect bosutinib isomer - Medchem Express erroneously sold by the 17 vendors as “Bosutinib Isomer 1”. - Reliable ChemTech • We have obtained unambiguous proof of the structure of Bosutinib Isomer 1 via X-ray crystallography, and we now offer - Santa Cruz Biotechnology this compound for sale under a new name and catalog number - Selleck Chemicals (Bosutinib Isomer 1, Free Base, B-1722 on page 13). Please see that - Symansis NZ Ltd. product page for further information, sizes and prices. - Synkinase • An 18th vendor has also sold incorrect bosutinib, specifically - Wuhan Sunrise to the laboratory headed by Prof. Stefan Knapp. The incorrect version of bosutinib sold by this vendor has been unambiguously - Xingcheng Chempharm proven to be different from bosutinib, but its actual structure has An 18th vendor has also erroneously sold an incorrect not yet been established. isomer of bosutinib. Published information and private communications we have received from Prof. Stefan Knapp’s laboratory indicate that an 18th vendor, “Company A”, also provided an incorrect isomer of bosutinib to the biochemical research reagents marketplace, specifically to the Knapp laboratory and perhaps to other laboratories. The Knapp group used the material from Company A in an X-ray crystallography study proving that the compound

12 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

from Company A was not the correct bosutinib isomer. This found on the Certificate of Analysis for each lot. The presence of X-ray study clearly distinguishes Company A’s product from solvent or water of crystallization affect the nominal molecular correct bosutinib, but the data obtained apparently could not weight but not the biological properties of the bosutinib product. conclusively establish the structure of the incorrect compound. • Sold for laboratory or manufacturing purposes only; not for Contrary to an erroneous report in Chemical and Engineering human, medical, veterinary, food, or household use. News, Company A is not Calbiochem, the latter having • This product is offered for R&D use in accordance with (i) 35 issued a public statement on this topic (www.millipore.com/ USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese antibodies/flx4/bosutinib_inhibitor_announcement). We have Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent not yet received permission from the Knapp laboratory to Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. release the name of Company A. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) NOTE: The 17 vendors listed above all sold a compound that and other common law exemptions of Canadian patent law; (vi) LC Labs now makes available under the name “Bosutinib Section 68B of the Patents Act of 1953 in New Zealand together Isomer 1” (Cat. No. B-1722 on page 13), for which we have with the amendment of same by the Statutes Amendment Bill of unambiguously proven the structure by X-ray crystallography. 2002; (vii) such related legislation and/or case law as may be or Unpublished kinase assay data obtained by our parent become applicable in the aforementioned countries; and (viii) such company, PKC Pharmaceuticals, Inc., indicate that bosutinib similar laws and rules as may apply in various other countries. and the incorrect isomer have significantly different kinase • Not available in some countries; not available to some institutions; inhibitory properties (manuscript in preparation). not available for some uses. • LCL-XP™: LC Labs X-ray Proven Structure™. The chemical H C 3 structure of our new bosutinib has been unambiguously proven by N

single-crystal X-ray crytallography. N O N • Bosutinib (SKI-606) is a novel tyrosine kinase inhibitor, more potent than imatinib. Bosutinib can overcome not only Bcr-Abl- O dependent mechanisms of resistance, but also those that are N CH NH O Bcr-Abl-independent. It is used to treat patients with chronic 3 CH myelogenous leukemia (CML) who demonstrate resistance to 3 imatinib or develop resistance during treatment. Jabbour, E. et al., Cl Cl “New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.” B-1722 Bosutinib Isomer 1, Free Base, >99% Semin. Hematol. 44: 25‑31 (2007). (LCL-XP™: LC Labs X-ray Proven Structure™) • Bosutinib is an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines and transfectants. The IC50 Size US$ ¤ £ ¥ values are in the low nanomolar range, which is 10- to 100-fold lower than those obtained with imatinib. Bosutinib has activity 25 mg 37 30 24 2,900 in cells where resistance to imatinib resulted from BCR-ABL 50 mg 55 45 35 4,300 gene amplification and in three of four Bcr-Abl point mutants 100 mg 89 72 57 7,000 examined. In in vivo experiments bosutinib retains activity in 200 mg 164 133 105 12,800 models where resistance is not caused by mutations, as well as in 500 mg 388 316 247 30,400 cells carrying the Y253F, E255K, and D276G mutations. Bosutinib 1 g 687 559 438 53,800 binds to a different conformation of Bcr-Abl than does imatinib. 2 g 1275 1037 813 99,800 Puttini, M. et al., “In vitro and in vivo activity of SKI-606, a novel NOTE: Euro, Pound and Yen prices are revised regularly. Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic Please visit www.LCLabs.com for our current prices. cells.” Cancer Res. 66: 11314‑11322 (2006). M.W. 530.45 c H Cl N O [1391063-17-4] • Bosutinib inhibits tumor cell proliferation, angiogenesis, growth 26 29 2 5 3 factor expression and Src-mediated signaling pathways in vivo. Storage: Store at or below -20 ºC. Solubility: Soluble in Jallal, H. et al., “A Src/Abl kinase inhibitor, SKI-606, blocks DMSO at 33 mg/mL; soluble in ethanol at 10 mg/ml with breast cancer invasion, growth, and metastasis in vitro and in warming; very poorly soluble in water; maximum solubility vivo.” Cancer Res. 67: 1580‑1588 (2007). in plain water is etimated to be about 10-50 µM; buffers, serum, or other additives may increase or decrease the • Bosutinib inhibited src-dependent activation of beta-catenin and aqueous solubility. Disposal: A blocked beta-catenin nuclear function by reducing its binding to the TCF4 transcription factor and its trans-activating ability in • PLEASE NOTE: our firm DID NOT synthesize the incorrect colorectal cancer cells. Coluccia, A.M. et al., “SKI-606 decreases bosutinib isomer that has been widely sold in the research growth and motility of colorectal cancer cells by preventing reagents marketplace, and we are NOT the cause of the pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin overall bosutinib problem. Please visit www.pkcpharma. and its nuclear signaling.” Cancer Res. 66: 2279‑2286 (2006). com/TwoOrMoreBosutinibs.html for extensive information about this problem. For a short synopsis of changes in LC • Bosutinib inhibited Src autophosphorylation in HT29 cells Laboratories’ products, product name, and catalog numbers, (IC = 0.25 µM). Although submicromolar concentrations of 50 please visit www.lclabs.com/PRODFILE/A-C/B-1709.php4. bosutinib inhibited HT29 cell colony formation in soft agar, antiproliferative activity on plastic did not correlate with Src • This compound, which we now sell under the name Bosutinib Isomer 1, is an incorrect isomer of bosutinib. X-ray, NMR and inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 µM, respectively). Golas, J.M. et al., “SKI-606, a Src/Abl melting point data that our firm has obtained indicate that inhibitor with in vivo activity in colon tumor xenograft models.” the following 17 vendors have erroneously sold this compound Cancer Res. 65: 5358‑5364 (2005). to one or more normal customers in the biochemical reagent marketplace, under the name “bosutinib” (please visit www. • We note that bosutinib is offered for sale by another vendor under pkcpharma.com/TwoOrMoreBosutinibs.html for extensive the name “Bosutinib Methanoate”, by which they probably mean additional information about this problem): “methanolate” (“methanoate” means “formate ester”, which is definitely not correct here). This “methanolate” nomenclature is - AK Scientific somewhat ambiguous because “methanolate” is often taken to - Alfa Aesar mean “methoxide anion” (not correct here) rather than “a molecule - Axon Medchem of neutral methanol included as solvent of crystallization with the - B-Bridge International primary compound” as presumably intended by this other vendor. The level of solvent or water, if any, in our bosutinib product is - Biorbyt Ltd.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 13 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

- Biovision Inc. B-8500 Brefeldin A, >99% - Eton Bioscience [Ascotoxin] [BFA] [Cyanein] [Decumbin] - LC Laboratories (part of PKC Pharma) - LKT Laboratories Size US$ ¤ £ ¥ - Medchem Express 10 mg 45 34 29 4,400 - Reliable ChemTech 25 mg 82 61 53 8,100 - Santa Cruz Biotechnology 50 mg 142 106 91 14,000 - Selleck Chemicals 100 mg 199 149 128 19,600 - Symansis NZ Ltd. 300 mg 555 415 356 54,800 1 g 1380 1031 886 136,200 - Synkinase NOTE: Euro, Pound and Yen prices are revised regularly. - Wuhan Sunrise Please visit www.LCLabs.com for our current prices. - Xingcheng Chempharm M.W. 280.36 c16H2404 [20350-15-6] An 18th vendor has also erroneously sold an incorrect M.I. 11: 1363 isomer of bosutinib. Published information and private Warning: Toxic. communications we have received from Prof. Stefan

Knapp’s laboratory indicate that an 18th vendor, “Company Storage: Store at or below -20 °C. Solubility: Soluble in A”, also provided an incorrect isomer of bosutinib to the DMSO at 100 mg/mL; soluble in ethanol at 25 mg/mL with biochemical research reagents marketplace, specifically to slight warming; very poorly soluble in water; maximum the Knapp laboratory and perhaps to other laboratories. solubility in plain water is estimated to be about 50-100 The Knapp group used the material from Company A in µM; buffers, serum, or other additives may increase or an X-ray crystallography study proving that the compound decrease the aqueous solubility. Disposal: A from Company A was not the correct bosutinib isomer. This X-ray study clearly distinguishes Company A’s product from • Specifically and reversibly blocks translocation of proteins correct bosutinib, but the data obtained apparently could not from the endoplasmic reticulum to the Golgi apparatus. conclusively establish the structure of the incorrect compound. Misumi, Y. et al., “Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes.” Contrary to an erroneous report in Chemical and Engineering J. Biol. Chem. 261: 11398‑11403 (1986). News, Company A is not Calbiochem, the latter having issued a public statement on this topic (www.millipore.com/ • Brefeldin A has been shown to induce apoptosis in human antibodies/flx4/bosutinib_inhibitor_announcement). We have tumor cells via a process requiring caspase activation. not yet received permission from the Knapp laboratory to Guo, H. et al., “Brefeldin A-mediated apoptosis requires release the name of Company A. the activation of caspases and is inhibited by Bcl-2.” Exp. Cell Res. 245: 57‑68 (1998). NOTE: The erroneous compound that the 17 vendors listed above all sold is the compound described on this page, namely • Brefeldin A has been identified as an activator of the “Bosutinib Isomer 1”, for which we have unambiguously sphingomyelin signal transduction cycle. Linardic, C. M. proven the structure by X-ray crystallography. et al., “Activation of the sphingomyelin cycle by brefeldin A: effects of brefeldin A on differentiation and implications • LCL-XP™: LC Labs X-ray Proven Structure™. The chemical for a role for ceramide in regulation of protein trafficking.” structure of our bosutinib isomer 1 has been unambiguously Cell Growth Differ. 7: 765‑774 (1996). Alessenko, A. V., proven by single-crystal X-ray crytallography. “The role of sphingomyelin cycle metabolites in transduction • We now sell the correct bosutinib isomer under the name of signals of cell proliferation, differentiation and death.” “Bosutinib, Free Base” (Cat. No. B-1788 on page 12). Membr. Cell Biol. 13: 303‑320 (2000). • Unpublished kinase assay data obtained by our parent company, • Sold for laboratory or manufacturing purposes only; not for PKC Pharmaceuticals, Inc., indicate that bosutinib and this human, medical, veterinary, food, or household use. incorrect isomer have significantly different kinase inhibitory properties (manuscript in preparation). OH H O O H C CH 3 3 N

N O N HO H H

O N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, N CH NH Cl Di-HCl Salt — see H-89, Dihydrochloride Salt 3 (Cat. No. H-5239 on page 52).

O

Cl CH 3

14 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

B-6697 Bryostatin 1, >99% B-3517 Bryostatin 2, >99% [B705008K112] Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 10 µg 83 58 50 7,800 10 µg 61 45 38 4,700 25 µg 159 111 96 15,000 25 µg 118 86 74 9,200 100 µg 375 261 227 35,400 NOTE: Euro, Pound and Yen prices are revised regularly. 100 µg 298 218 188 23,100 Please visit www.LCLabs.com for our current prices. 300 µg 720 527 453 55,900 1 mg 2190 1604 1378 170,000 M.W. 863.00 c45H66O16 [87745-28-6] NOTE: Euro, Pound and Yen prices are revised regularly. Note: Binds to glass and plastic surfaces in aqueous Please visit www.LCLabs.com for our current prices. solutions.

M.W. 905.03 c47H68O17 [83314-01-6] Storage: Store at or below -20 °C. Solubility: Soluble in M.I. 14: 1457 DMSO and ethanol. Disposal: A

Note: Binds to glass and plastic surfaces in aqueous • Protein kinase C activator exhibiting a Ki value 1 order of solutions. magnitude higher than bryostatin 1. Inhibits DNA synthesis at 100 Storage: Store at or below -20 °C. Solubility: Soluble in nM in SH-SY5Y human neuroblastoma cells. Jalava, A.M. et al., DMSO and ethanol. Disposal: A “Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells.” • Bryostatin 1 binds to and activates protein kinase C, but its Cancer Res. 50: 3422‑3428 (1990). biological effects differ greatly from those induced by other • Has somewhat different effect on various cells and tissues protein kinase C activators. Bryostatin 1 fails to mimic many than bryostatin 1. See Technical Note #1 for more technical effects caused by PMA and actually blocks some PMA- information. induced responses in a variety of cells and tissues. Kraft, A.S. et al., “Bryostatin, an activator of the calcium phospholipid- • Sold for laboratory or manufacturing purposes only; not for dependent protein kinase, blocks phorbol ester-induced human, medical, veterinary, food, or household use. differentiation of human promyelocytic leukemia cell HL-60.” HO Proc. Natl. Acad. Sci. USA 83: 1334‑1338 (1986). Sako, T. et al., OH MeO C “Partial parallelism and partial blockade by bryostatin 1 of effects 2 of phorbol ester tumor promoters on primary mouse epidermal OO cells.” Cancer Res. 47: 5445‑5450 (1987). Dell’Aquila, M.L. et al., “Inhibition by bryostatin 1 of the phorbol ester-induced O blockage of differentiation in hexamethylene bisacetamide-treated OH OH O O Friend erythroleukemia cells.” Cancer Res. 47: 6006‑6009 (1987). Hess, A.D. et al., “Activation of human T lymphocytes by C H bryostatin.” J. Immunol. 141: 3263‑3269 (1988). 3 7 O HO

• The true affintiy of bryostatin 1 for the PDBu binding site on O CO Me PKC appears to be in the low picomolar range or lower. de 2 Vries, D.J. et al., “Demonstration of sub-nanomolar affinity BSI-201 – see Iniparib (Cat. No. I-5432 on page 56). of bryostatin 1 for the phorbal ester receptor in rat brain.” Biochem. Pharmacol. 37: 4069‑4073 (1988). “C-kinase...” entries appear under “Protein Kinase C....” • Please request Technical Note #1 for extensive technical “Ca2+/phospholipid-dependent Protein Kinase...” entries appear information. under “Protein Kinase C....” • Please note: The correct molecular weight for bryostatin 1 is 905.04. Perhaps the M.W. 887 error found in other catalogs arises C-2581 Cabazitaxel, >99% because the original publication describing bryostatin 1 mentions a Synonyms: [RPR-116258] [Taxoid XRP6258] mass spectrum peak at 887, but apparently that peak resulted from [TXD-258] [XRP-6258] the loss of one water molecule during the mass spectral process. Related Terms: [Jevtana] • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. Size US$ ¤ £ ¥ 5 mg 52 38 31 6,300 HO OAc MeO C Prices 10 mg 81 60 48 9,700 2 Reduced! 25 mg 124 92 73 14,900 OO 50 mg 179 132 106 21,500 O 100 mg 247 182 146 29,700

OH OH 200 mg 434 321 256 52,200 O O 500 mg 917 677 540 110,200 1 g 1680 1241 990 201,900 C H O HO 3 7 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. O CO Me 2 M.W. 835.93 c45H57NO14 [183133-96-2] M.I. 14: 10493 Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 50 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 1-2 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 15 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Cabazitaxel, also known as XRP-6258, is a second-generation CH semi-synthetic derivative of paclitaxel, a natural taxoid O 3 O CH O H C CH microtubule inhibitor. Paller, C.J. and Antonarakis, E.S., 3 O 3 3 H C 3 CH CH O “Cabazitaxel: a novel second-line treatment for metastatic 3 3 H C 3 O N O castration-resistant prostate cancer.” Drug Des. Devel. Ther. CH 5: 117‑124 (2011). H OH 3 HO H • In preclinical studies, cabazitaxel was shown to have antitumor O O activity in a variety of docetaxel-refractory in vitro and in vivo O O CH models. Bissery, M.C. et al., “Preclinical evaluation of TXD258, 3 a new taxoid.” Proceedings of the American Association for O Cancer Research Abstract 411364 (2000). Vrignaud, P. et al., “In vivo efficacy of TXD258, a new taxoid, against human tumor xenografts.” Proceedings of the American Association for Cancer Caelyx – see Doxorubicin, Hydrochloride Salt Research Abstract 411365 (2000). (Cat. No. D-4000 on page 33) and see its active ingredient, namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). • 755 participants with metastatic castration-resistant prostate cancer who had received previous hormone therapy were CAFdA – see Clofarabine, Free Base (Cat. No. C-1999 on page 22). treated with prednisone daily, and were randomly allocated to treatment groups (377 mitoxantrone and 378 cabazitaxel). “Calcium/phospholipid-dependent Protein Kinase...” entries appear under “Protein Kinase C...” Median survival was 15.1 months in the cabazitaxel group and 12.7 months in the mitoxantrone group. Median progression-free C-3987 Calyculin A, >98% survival was 2.8 months in the cabazitaxel group and 1.4 months in the mitoxantrone group. de Bono, J.S. et al., “Prednisone Size US$ ¤ £ ¥ plus cabazitaxel or mitoxantrone for metastatic castration- 25 µg 89 68 56 7,100 resistant prostate cancer progressing after docetaxel treatment: a 50 µg 137 104 87 10,900 randomised open-label trial.” Lancet 376: 1147‑1154 (2010). 100 µg 229 174 145 18,200 • When compared with docetaxel and paclitaxel, cabazitaxel was 300 µg 585 445 369 46,600 reported to have poor affinity for the ATP-dependent drug efflux pump, P-glycoprotein 1 (P-gp), and greater penetration of the 1 mg 1675 1274 1058 133,300 NOTE: Euro, Pound and Yen prices are revised regularly. blood-brain barrier. Mita, A.C. et al. “Phase I and pharmacokinetic Please visit www.LCLabs.com for our current prices. study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid M.W. 1009.17 C50H81N4O15P [101932-71-2] tumors.” Clin. Cancer Res. 15: 723‑730 (2009). M.I. 14: 1724 • Brain uptake of cabazitaxel was increased when concentrations SPECIAL HAZARD: TUMOR PROMOTER. Gloves and exceeded 11 µM and the saturation was found to be at 13 µM, mask should be worn when using this compound. Care suggesting the role of a critical transporter (that is, P-gp) in must be taken to prevent contact through all routes of transporting cabazitaxel across the blood-brain barrier upon a exposure. certain threshold. Cisternino, S. et al., “Nonlinear accumulation NOTE: Do not expose to sunlight or fluorescent lights for in the brain of the new taxoid TXD258 following saturation extended periods. of P-glycoprotein at the blood-brain barrier in mice and rats.” Br. J. Pharmacol. 138: 1367‑1375 (2003). Storage: Store at or below -20 °C. Solubility: Soluble in DMSO and ethanol; very poorly soluble in water; maximum • Cabazitaxel is the active ingredient in the drug product sold under ® solubility in plain water is estimated to be about 1-10 the trade name Jevtana . This drug is currently approved in at least µM; buffers, serum, or other additives may increase or one country for use in patients with hormone-refractory metastatic decrease the aqueous solubility. Disposal: A prostate cancer. NOTE: THE CABAZITAXEL RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT • Very potent inhibitor (Ki = ca. 0.1 nM) with high JEVTANA® AND IS NOT FOR HUMAN USE. specificity for the PP-1 and PP-2 classes of protein • Another CAS number previously assigned to cabazitaxel, namely serine/threonine phosphatase. Ishihara, H. et al. 890654-44-1, has been deleted by CAS and is no longer in use. Biochem. Biophys. Res. Comm. 159: 871‑877 (1989). • Sold for laboratory or manufacturing purposes only; not for • Potent non-phorbol type tumor promoter. Suganuma, M. et al. human, veterinary, food, or household use. Cancer Res. 50: 3521‑3525 (1990). • This product is offered for R&D use in accordance with (i) 35 • Please request Technical Note #19 for additional information. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Sold for laboratory or manufacturing purposes only; not for Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent human, medical, veterinary, food, or household use. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. OH O Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) O and other common law exemptions of Canadian patent law; (vi) H CO N 3 H Section 68B of the Patents Act of 1953 in New Zealand together N OH N H C CH with the amendment of same by the Statutes Amendment Bill of 3 3 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such OH similar laws and rules as may apply in various other countries. HO O P • Not available in some countries; not available to some institutions; O O OH not available for some uses. O N

C OH OH OCH3

Campto – see its active ingredient, namely Irinotecan, Hydrochloride Salt, Trihydrate (Cat. No. I-4122 on page 57).

16 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Not available in some countries; not available to some institutions; Camptosar – see its active ingredient, namely Irinotecan, Hydrochloride Salt, Trihydrate (Cat. No. I-4122 on page 57). not available for some uses. Camptothesin 11 – see Irinotecan, Hydrochloride Salt, O Trihydrate (Cat. No. I-4122 on page 57). N O N

C-1201 Canertinib, Dihydrochloride Salt, >99% N . 2HCl NH

[CI-1033] [PD183805] NH O Size US$ ¤ £ ¥ 10 mg 29 22 19 3,200 F 25 mg 48 37 32 5,400 Cl 50 mg 77 60 51 8,600 Capecitabin – see Capecitabine (Cat. No. C-2799 on page 17). 100 mg 114 88 75 12,700 200 mg 197 152 130 22,000 C-2799 Capecitabine, >99% 1 g 865 669 572 96,700 [Capecitabin] [Capecitibine] [Capecytabine] NOTE: Euro, Pound and Yen prices are revised regularly. [Capiibine] [Captabin] [Caxeta] [Ro 09-1978] Please visit www.LCLabs.com for our current prices. [Ro 09-1978/000] [Xabine] [Xeloda] M.W. 558.86 c24H25ClFN5O3•2HCl [289499-45-2] M.I. 14: 1744 Size US$ ¤ £ ¥ 1 g 46 36 30 5,100 Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 1 mg/mL with 2 g 84 65 56 9,400 warming; soluble in water at 10 mg/mL with warming; 5 g 155 120 102 17,300 buffers, serum, or other additives may increase or 10 g 270 209 178 30,200 decrease the aqueous solubility. Compound is somewhat 25 g 645 499 426 72,100 unstable in HPLC sample solution at room temperature. 50 g 1170 904 773 130,800 Disposal: A 100 g 2190 1693 1448 244,800 • Canertinib (CI-1033, PD 183805) is a pan-erbB tyrosine kinase NOTE: Euro, Pound and Yen prices are revised regularly. inhibitor. It selectively inhibits erbB1 (epidermal growth factor Please visit www.LCLabs.com for our current prices. receptor), erbB2, erbB3, and erbB4 without blocking tyrosine M.W. 359.35 c H FN O [154361-50-9] kinase activity of many other receptors such as platelet-derived 15 22 3 6 growth factor receptor, fibroblast growth factor receptor, and Storage: Store at or below -20 ºC. Solubility: Soluble insulin receptor. Slichenmyer, W.J. et al., “CI-1033, a pan-erbB in DMSO at 100 mg/mL; soluble in ethanol at 12.5 mg/ tyrosine kinase inhibitor.” Semin. Oncol. 28: 80‑85 (2001). mL with slight warming; soluble in water at 2 mg/mL with slight warming; buffers, serum, or other additives may • Canertinib is an irreversible tyrosine kinase inhibitor. It not increase or decrease the aqueous solubility. Disposal: A only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent • Capecitabine is a pre-prodrug of 5-fluorouracil (5-FU). After intracellular destruction of ErbB-2 molecules. Canertinib alkylates oral uptake, capecitabine is first metabolized to 5'-deoxy-5- a cysteine residue specific to ErbB receptors. The degradative fluorocytidine (5'-DFCR), which happens mainly in the liver pathway of ErbB receptor tyrosine kinases stimulated by tyrosine by carboxyl-esterase. The metabolite is converted to 5'-deoxy- kinase inhibitors appears to be chaperone mediated, and thus 5-fluoro-uridine (5'-DFUR) by cytidine deaminase in liver and is similar to the pathways activated by the heat shock protein tumor tissue. Then 5'-DFUR is converted to 5-FU intracellularly 90 (Hsp90) antagonist geldanamycin and by stress-induced by thymidine phosphorylase, which is often expressed in tumor mechanisms. Citri, A. et al., “Drug-induced ubiquitylation and tissue. Miwa, M. et al., “Design of a novel oral fluoropyrimidine degradation of ErbB receptor tyrosine kinases: implications for carbamate, capecitabine, which generates 5-fluorouracil cancer therapy.” EMBO J. 21: 2407‑2417 (2002). selectively in tumours by enzymes concentrated in human liver and cancer tissue.” Eur. J. Cancer 34: 1274‑1281 (1998). • Increases the effectiveness of radiation therapy. Nyati, M.K. et al., “Radiosensitization by pan ErbB inhibitor CI-1033 in vitro and • Capecitabine inhibits tumor growth by incorporation of 5-FU in vivo.” Clin Cancer Res. 10: 691‑700 (2004). into RNA and DNA and inhibition of thymidylate synthase. Schellens, J.H., “Capecitabine.” Oncologist 12: 152‑155 (2007). • Prevents smallpox viral replication in vitro and inhibits smallpox • Capecitabine is the active ingredient in the drug sold under the viral infection in vivo. Fauci, A.S. and Challberg, M.D., “Host- ® based antipoxvirus therapeutic strategies: turning the tables.” trade name Xeloda . The drug is currently approved in at least one J. Clin. Invest. 115: 231‑233 (2005). country for use in patients with metastatic breast and colorectal cancers. NOTE: The capecitabine product sold by LC Laboratories • Canertinib inhibited erbB receptor phosphorylation and induced is NOT Xeloda® and is NOT for human use. growth inhibition and apoptosis at concentrations of 1 µM or more. Hughes, D.P. et al., “Essential erbB family phosphorylation • Other CAS numbers previously assigned to capecitabine, in osteosarcoma as a target for CI-1033 inhibition.” 158798‑73‑3 and 958887‑39‑3, have been deleted by CAS and are Pediatr. Blood Cancer. 46: 614‑623 (2006). no longer in use. • Sold for laboratory or manufacturing purposes only; not for • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. similar laws and rules as may apply in various other countries.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 17 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; patients with relapsed and/or refractory multiple myeloma." not available for some ues. Blood 119: 5661‑5670 (2012). • Carfilzomib is the active ingredient in the drug product sold under H CH O 3 ® OH N O the trade name Kyprolis . This drug is currently approved in N at least one country for use in patients with multiple myeloma. HO N O NOTE: THE CARFILZOMIB RESEARCH COMPOUND SOLD ® O F BY LC LABORATORIES IS NOT KYPROLIS AND IS NOT H C FOR HUMAN USE. 3 • Sold for laboratory or manufacturing purposes only; not for Capecitibine – see Capecitabine (Cat. No. C-2799 on page 17). human, veterinary, food, or household use. Capecytabine – see Capecitabine (Cat. No. C-2799 on page 17). • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Capiibine – see Capecitabine (Cat. No. C-2799 on page 17). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent C-2799-2009-10-08-kedREV.SKC Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Captabin – see Capecitabine (Cat. No. C-2799 on page 17). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) C-3022 Carfilzomib, Free Base, >99% and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Synonyms: [PR-171] with the amendment of same by the Statutes Amendment Bill of Related Terms: [Kyprolis] 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such Size US$ ¤ £ ¥ similar laws and rules as may apply in various other countries. 5 mg 38 27 23 4,300 • Not available in some countries; not available to some institutions; New! 10 mg 49 35 29 5,600 not available for some uses. 25 mg 94 68 56 10,700 50 mg 123 88 74 14,000 100 mg 211 152 127 24,000 200 mg 327 235 196 37,100 NOTE: Euro, Pound and Yen prices are revised regularly. O O O O H H Please visit www.LCLabs.com for our current prices. N N N N N O M.W. 719.91 C H N O [868540-17-4] H H CH 40 57 5 7 O O 3 CH CH M.I. 15: 1837 3 3 CH CH Storage: Store at or below -20 ºC. Solubility: Soluble in 3 3 DMSO at 80 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility C-2662 Carnosic Acid, Free Acid, >99% in plain water is estimated to be about 1-5 µM; buffers, serum, or other additives may increase or decrease the Synonyms: [Salvin] aqueous solubility. Disposal: A Related Terms: [Rosamox] [RoseOx] • Carfilzomib, also known as PR-171, is an irreversible, Size US$ ¤ £ ¥ epoxomicin-related proteasome inhibitor. It potently bound to and specifically inhibited the chymotrypsin-like proteasome (ChT-L) 25 mg 77 55 46 8,700 and immunoproteasome activities in the β5 subunit with >80% New! 50 mg 119 86 71 13,500 inhibition at doses of ≥10 nM. It showed little or no effect on 100 mg 179 129 108 20,300 the postglutamyl peptide hydrolyzing (PGPH) activity in the β1 250 mg 365 262 219 41,500 subunit and trypsin-like (T-L) activity in the β2 subunit at doses 500 mg 488 351 293 55,400 of ≤100 nM in vitro. It also inhibited the proliferation of IL-6- 1 g 685 492 411 77,800 independent and -dependent myeloma cell lines with an IC50 NOTE: Euro, Pound and Yen prices are revised regularly. of <5 nM in both and ultimately led to apoptosis. Carfilzomib Please visit www.LCLabs.com for our current prices. demonstrated higher efficacy compared with bortezomib (please M.W. 332.43 c H O [3650-09-7] see Bortezomib, Free Base, Cat. No. B-1408 on page 11) and was 20 28 4 active against bortezomib-resistant MM cell lines and samples M.I. 15: 1850 from patients with clinical bortezomib resistance. Furthermore, Storage: Store at or below -20 ºC. Solubility: Soluble in carfilzomib overcame resistance to other conventional DMSO. Disposal: A agents. Kuhn, D.J. et al., "Potent activity of carfilzomib, • Carnosic acid is a "pro-electrophilic" compound, that is, one that a novel, irreversible inhibitor of the ubiquitin-proteasome remains non-reactive until it is converted to an electrophile by pathway, against preclinical models of multiple myeloma." an oxidative reaction at or near the intended target site. Carnosic Blood 110: 3281‑3290 (2007). acid inhibited lipopolysaccharide (LPS) induced expression and • Coadministration of carfilzomib with the histone deacetylase release of IL-1β and IL-6 (typical inflammatory cytokines) from inhibitor vorinostat (please see Vorinostat, Cat. No. V-8477 on microglial cells in vitro. Yanagitai, M. et al., "Carnosic acid, a page 124) resulted in sharp increases in mitochondrial injury and pro-electrophilic compound, inhibits LPS-induced activation of apoptosis in multiple mantle cell lymphoma (MCL) cell lines microglia." Biochem. Biophys. Res. Commun. 418: 22‑26 (2012). and primary MCL cells. Carfilzomib/vorinostat coadministration • Carnosic acid significantly protected retina-derived cell lines also induced a pronounced reduction in tumor growth compared against H2O2-induced toxicity in vitro. It also protected retinas with single agent treatment in an MCL xenograft model. from light-induced retinal degeneration in vivo. Rezaie, T. Dasmahapatra, G. et al., "Carfilzomib interacts synergistically et al., "Protective effect of carnosic acid, a pro-electrophilic with histone deacetylase inhibitors in mantle cell lymphoma cells compound, in models of oxidative stress and light-induced retinal in vitro and in vivo." Mol. Cancer Ther. 10: 1686‑1697 (2011). degeneration." Invest. Ophthalmol. Vis. Sci. 53: 7847‑7854 (2012). • The response data for single-agent carfilzomib were very • Coadministration of the vitamin D analog known as "Gemini- promising in bortezomib-naive patients with relapsed and/ 19-nor" and standardized rosemary extract to leukemia-bearing or refractory multiple myeloma in a phase 2 clinical trial. mice resulted in a synergistic increase in survival of mice with Vij, R. et al., "An open-label, single-arm, phase 2 (PX-171- systemic acute myeloid leukemia. Shabtay, A. et al., "Synergistic 004) study of single-agent carfilzomib in bortezomib-naive

18 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

antileukemic activity of carnosic acid-rich rosemary extract and membrane, thus controlling edema. Kamoun, W.S. et al., “Edema the 19-nor Gemini vitamin D analogue in a mouse model of control by cediranib, a vascular endothelial growth factor receptor- systemic acute myeloid leukemia." Oncology 75: 203‑214 (2008). targeted kinase inhibitor, prolongs survival despite persistent brain • Carnosic acid is the active ingredient in the drug product sold tumor growth in mice.” J. Clin. Oncol. 27: 2542‑2552 (2009). under the trade names Rosamox™ and RoseOx®. NOTE: THE • Hypertension induced by cediranib is reported to be manageable. Carnosic acid RESEARCH COMPOUND SOLD BY LC Langenberg, M.H. et al., “Effective strategies for management of LABORATORIES IS Neither Rosamox™ nor RoseOx® hypertension after vascular endothelial growth factor signaling AND IS NOT FOR HUMAN USE. inhibition therapy: results from a phase II randomized, factorial, • Sold for laboratory or manufacturing purposes only; not for double-blind study of Cediranib in patients with advanced solid human, veterinary, food, or household use. tumors.” J. Clin. Oncol. 27: 6152‑6159 (2009).

OH CH • Cediranib demonstrated potent antitumor and antiangiogenic 3 efficacy in the murine renal cell carcinoma model. HO CH Medinger, M. et al., “Antitumor and antiangiogenic activity 3 HOOC of cediranib in a preclinical model of renal cell carcinoma.” Anticancer Res. 29: 5065‑5076 (2009). • Combined treatments of cediranib with radiation in Calu-6 H lung xenografts induced a significantly enhanced growth delay H C CH 3 3 when compared with either modality alone. Williams, K.J. et al., “Inhibition of vascular endothelial growth factor signalling using Caspase Inhibitor VI – see Z-VAD-FMK, Free Acid cediranib (RECENTIN; AZD2171) enhances radiation response (Cat. No. Z-9999 on page 127). and causes substantial physiological changes in lung tumour Caxeta – see Capecitabine (Cat. No. C-2799 on page 17). xenografts.” Br. J. Radiol. 81: S21‑S27 (2008). CCG-168 – see AZD8055, Free Base (Cat. No. A-2345 on page 8). • Cediranib reverses ABCB1 (P-glycoprotein)- and ABCC1 (MRP1)-mediated multidrug resistance by directly inhibiting CCI-779 — see Temsirolimus (Cat. No. T-8040 on page 111). their drug efflux function. Tao, L.Y. et al., “Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated C-4300 Cediranib, Free Base, >99% multidrug resistance by inhibition of their transport function.” Synonyms: [AZD2171] Cancer Chemother. Pharmacol. 64: 961‑969 (2009). Related Terms: [Recentin] • Cediranib is the active ingredient in the drug formulation designated by the trade name Recentin®. This drug has been in Size US$ ¤ £ ¥ human clinical trials for use in patients with non-small cell lung 5 mg 62 48 41 6,900 cancer, small cell lung cancer, kidney cancer, colorectal cancer, 10 mg 97 75 64 10,800 breast cancer, liver and ovarian cancer, melanoma, mesothelioma, and glioblastoma. NOTE: THE CEDIRANIB, FREE BASE 25 mg 135 104 89 15,100 RESEARCH COMPOUND SOLD BY LC LABORATORIES IS 50 mg 195 151 129 21,800 NOT RECENTIN® AND IS NOT FOR HUMAN USE. 100 mg 276 213 182 30,900 • Related CAS numbers: 857036-77-2 for the cediranib maleate. 200 mg 515 398 340 57,600 • Other CAS numbers previously assigned to cediranib, namely 300 mg 720 557 476 80,500 557795-03-6 and 790713-41-6, have been deleted by CAS and are NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. no longer in use. • Sold for laboratory or manufacturing purposes only; not for M.W. 450.51 c H FN O [288383-20-0] 25 27 4 3 human, veterinary, food, or household use. Storage: Store at or below -20 ºC. • This product is offered for R&D use in accordance with (i) 35 Solubility: Soluble in DMSO. Disposal: A USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Cediranib is a highly potent inhibitor of recombinant KDR Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. tyrosine kinase activity in vitro (IC50 < 1 nM). Inhibitory activity was also observed against the kinase associated with Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Flt-1 (IC = 5 nM), the VEGF-C and VEGF-D receptor Flt‑4 and other common law exemptions of Canadian patent law; (vi) 50 Section 68B of the Patents Act of 1953 in New Zealand together (IC ≤ 3 nM), recombinant PDGFR-related kinase c-Kit 50 with the amendment of same by the Statutes Amendment Bill of (IC50 = 2 nM), and PDGFRβ tyrosine kinase (IC50 = 5 nM). In HUVEC, it inhibited VEGF-stimulated phosphorylation of KDR, 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such c-Kit, PDGFR-α, PDGFR-β in a dose-dependent manner with IC50 values of 0.5, 1, 5, and 8 nM, respectively. It inhibited VEGF- similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; stimulated HUVEC proliferation potently with an IC50 value of 0.4 nM. Consistent with potent activity against VEGF signaling, not available for some uses.

cediranib inhibited vessel branching, length, and area in vitro with H IC values of 0.1, 0.1, and 0.2 nM, respectively. It also completely 50 N abolished VEGF-induced angiogenesis in vivo. However, it CH inhibited tumor cell proliferation in vitro only at comparatively 3 O high concentrations, showing IC50 values of 3.0 µM for SKOV‑3 H C O F 3 cells, 3.8 µM for MDA-MB-231 cells, 5.8 µM for PC-3 cells, N 6.4 µM for Calu-6 cells, and 7.4 µM for SW620 cells. It also inhibited the growth of these five tumor models in nude mice. N O N Furthermore, cediranib induced vascular regression in human lung tumor xenografts. Wedge, S.R. et al., “AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor Celebra – see Celecoxib (Cat. No. C-1502 on page 20). receptor-2 tyrosine kinase inhibitor for the treatment of cancer.” Cancer Res. 65: 4389‑4400 (2005). Celebrex – see its active ingredient, namely Celecoxib • Cediranib significantly increased survival of mice wth (Cat. No. C-1502 on page 20). glioblastoma by decreasing tumor vessel permeability, normalizing Celecox – see its active ingredient, namely Celecoxib perivascular cell coverage, and thinning of the basement (Cat. No. C-1502 on page 20).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 19 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) C-1502 Celecoxib, >99% and other common law exemptions of Canadian patent law; (vi) [Celebra] [Celebrex] [Celecox] [Onsenal] Section 68B of the Patents Act of 1953 in New Zealand together [SC-58635] [Solexa] [YM-177] with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or Size US$ ¤ £ ¥ become applicable in the aforementioned countries; and (viii) such 300 mg 66 51 44 7,400 similar laws and rules as may apply in various other countries. 1 g 89 69 59 10,000 • Not available in some countries; not available to some institutions; 5 g 325 251 215 36,300 not available for some uses.

10 g 520 402 344 58,100 F C 3 25 g 925 715 612 103,400 50 g 1430 1105 945 159,900 N 100 g 1780 1376 1177 199,000 N NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices.

M.W. 381.37 C17H14F3N3O2S [169590-42-5] M.I. 14: 1956 O S O NH Storage: Store at or below -20 ºC. Solubility: Soluble in 2 DMSO at 200 mg/mL; soluble in ethanol at 100 mg/mL; very poorly soluble in water; maximum solubility in plain CEP-18770 – see Delanzomib, Free Base water is estimated to be about 10-50 µM; buffers, serum, (Cat. No. D-4011 on page 28). or other additives may increase or decrease the aqueous Certican – see its active ingredient, namely Everolimus solubility. Disposal: A (Cat. No. E-4040 on page 40). • Celecoxib is a highly selective COX-2 inhibitor and primarily inhibits prostaglandin production. cFMS Receptor Tyrosine Kinase Inhibitor – see GW2580, Free Base (Cat. No. G-5903 on page 51). • Celecoxib is approximately 7.6-fold more selective for COX- 2 inhibition over COX-1. This specificity allows celecoxib to CGP 39360 – see Staurosporine (Cat. No. S-9300 on page 108). reduce inflammation and pain while minimizing gastrointestinal CGP 41251 – see PKC412 (Cat. No. P-7600 on page 91). adverse drug reactions (e.g. stomach ulcers) that are common with non-selective non-steroidal anti-inflammatory drugs (NSAIDs). CGP 79787 – see Vatalanib, Dihydrochloride Salt Silverstein, F.E. et al., “Gastrointestinal toxicity with celecoxib (Cat. No. V-8303 on page 120). vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized CGP-57148B – see Imatinib, Free Base (Cat. No. I-5577 on page 53) and Imatinib, Methanesulfonate Salt controlled trial. Celecoxib Long-term Arthritis Safety Study.” (Cat. No. I-5508 on page 54). JAMA 284: 1247‑1255 (2000). • Celecoxib and other COX-2 inhibitors increase the risk of CHEBI: 120185 — see Clofarabine, Free Base myocardial infarction. Caldwell, B. et al., “Risk of cardiovascular (Cat. No. C-1999 on page 22). events and celecoxib: a systematic review and meta-analysis.” CHIR 911 — see CHIR99021, Free Base J. R. Soc. Med. 99: 132‑140 (2006). (Cat. No. C-6556 on page 20). • COX-2 not only plays an important role in inflammation but also is involved in multiple biologic events throughout the tumorigenic CHIR-258 — see Dovitinib, Free Base (Cat. No. D-3608 on page 31) and Dovitinib, Lactate Salt (Cat. No. D-3699 on page 32). process. COX-2 inhibitors may act additively or synergistically with currently used cytotoxics and molecularly targeted agents C-6556 CHIR99021, Free Base, >99% to prevent and treat cancers. Koki, A.T. and Masferrer, J.L., “Celecoxib: a specific COX-2 inhibitor with anticancer Synonyms: [CHIR 911] [CT99021] properties.” Cancer Control 9: 28‑35 (2002). [GSK-3 Inhibitor XVI] • Celecoxib shows competitive kinetics on COX-1 (K i = 10-16 µM). Size US$ ¤ £ ¥ It also displays an initial competitive interaction with COX-2 (Ki = 11-15 µM), followed by a time-dependent interaction leading to 2 mg 48 37 32 4,600 potent inhibition and inactivation (Kinact = 0.03-0.5 s-1). Half- 5 mg 81 62 54 7,700 10 mg 121 93 80 11,500 maximal inhibition (IC50) using end-point assays demonstrates the competitive component on COX-1 (IC50 = 4-19 µM) and the 25 mg 218 167 144 20,800 inactivation component on COX-2 (IC50 = 0.003-0.006 µM). 50 mg 385 294 255 36,700 Gierse, J.K. et al., “Kinetic basis for selective inhibition of cyclo- 100 mg 637 487 421 60,700 oxygenases.” Biochem J. 339: 607-614 (1999). 200 mg 1125 860 744 107,200 • Celecoxib is the active ingredient in the drug sold under the trade NOTE: Euro, Pound and Yen prices are revised regularly. name Celebrex® or Celebra® in some countries. These drugs Please visit www.LCLabs.com for our current prices. are approved in at least one country for treatment of patients M.W. 465.34 c H Cl N [252917-06-9] with osteoarthritis, rheumatoid arthritis, acute pain, painful 22 18 2 8 menstruation and menstrual symptoms, and it is also used to Storage: Store at or below -20 ºC. reduce numbers of colon and rectum polyps in patients with Solubility: Soluble in DMSO at 25 mg/mL with familial adenomatous polyposis. NOTE: the celecoxib sold by warming; very poorly soluble in ethanol; very poorly ® ® LC Laboratories is NOT Celebrex or Celebra and is NOT for soluble in water; maximum solubility in plain water human use. is estimated to be about 20-40 µM; buffers, serum, • Sold for laboratory or manufacturing purposes only; not for or other additives may increase or decrease the human, medical, veterinary, food, or household use. aqueous solubility. +Disposal: A • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • CHIR99021 specifically inhibits glycogen synthase kinase-3β Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent (GSK3β, IC50 = 5 nm) and GSK3α (IC50 = 10 nm), inhibits Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. preadipocyte differentiation (IC50 = 0.3 µM), possibly by

20 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

blocking induction of C/EBPα and PPARγ, and mimics Wnt signaling in 3T3-L1 preadipocytes. Bennett, C.N. et al., C-2606 CI-994, Free Base, >99% (Tacedinaline) “Regulation of Wnt signaling during adipogenesis.” [Acetyldinaline] [Gö 5549] [Goe 5549] [PD 123654] J. Biol. Chem. 277: 30998‑31004 (2002). [Tacedinaline] • CHIR99021 showed highly selective inhibition of GSK-3α and Size US$ ¤ £ ¥ GSK-3β, with IC50s of 10 nM and 6.7 nM, respectively. It showed 50 mg 63 47 41 6,100 a Ki of 9.8 nM for GSK-3β. However, it exhibited an IC50 of 8800 nM for CDC2. CHIR99021 activates glycogen synthase 100 mg 89 67 57 8,600 in CHO-IR cells with EC50 of 763 nM. ZDF rats display insulin 300 mg 188 141 121 18,100 resistance, glucose intolerance, and mild hyperglycemia. In these 1 g 465 349 300 44,800 rats, a single oral dose of CHIR 99021 rapidly reduced plasma 5 g 1350 1012 871 129,900 glucose while plasma insulin remained at or below control NOTE: Euro, Pound and Yen prices are revised regularly. levels. ZDF rats treated with CHIR 99021 showed significantly Please visit www.LCLabs.com for our current prices. improved glucose tolerance with no significant differences M.W. 269.30 c H N O [112522-64-2] in plasma insulin levels compared with control animals. 15 15 3 2 Ring, D.B. et al., “Selective glycogen synthase kinase 3 inhibitors Storage: Store at or below -20 ºC. Solubility: Soluble in potentiate insulin activation of glucose transport and utilization DMSO at 66 mg/mL; very poorly soluble in ethanol; very in vitro and in vivo.” J. Biol. Chem. 277: 30998‑31004 (2002). poorly soluble in water; maximum solubility in plain water Diabetes 52: 588‑595 (2003). is estimated to be about 25-100 µM; buffers, serum, or • Alsterpaullone, kenpaullone, SB 214763, and SB 415286 not other additives may increase or decrease the aqueous only inhibited GSK-3 potently but also blocked CDKs. In solubility. Disposal: A contrast, CHIR99021 showed 350-fold selectivity toward GSK-3 • CI-994 is a histone deacetylase (HDAC) inhibitor and induces compared to CDKs. GSK-3 is an important intermediate in the histone hyperacetylation in living cells. CI-994 inhibited HDAC-1 pathway from the insulin receptor to the Thymine-rich Insulin and HDAC-2 but not the prototypical histone acetyltransferase Response Element (TIRE). Regulation of gene transcription by GCN5. Kraker, A.J. et al., “Modulation of histone acetylation by insulin totally depends on GSK-3 inhibition. Finlay, D. et al., [4-(acetylamino)-N-(2-amino-phenyl) benzamide] in HCT-8 colon “Glycogen synthase kinase-3 regulates IGFBP-1 gene carcinoma.” Mol. Cancer Ther. 2: 401‑408 (2003). transcription through the thymine-rich insulin response element.” • CI-994 in combination with traditional anti-cancer agents BMC Mol. Biol. 5: 15 (2004). cytarabine (ara-C), daunorubicin and mitoxantrone resulted in • CHIR99021 induced osteoblastogenesis, increased mineralization, a synergistic effect against acute myeloid leukemia (AML). and inhibited adipogenesis in ST2 cells. Bennett C.N. et al., Hubeek, I. et al., “CI-994 (N-acetyl-dinaline) in combination with “Regulation of osteoblastogenesis and bone mass by Wnt10b.” conventional anti-cancer agents is effective against acute myeloid Proc. Natl. Acad. Sci. USA 102: 3324‑3329 (2005). leukemia in vitro and in vivo.” Oncol. Rep. 19: 1517‑1523 (2008). • GSK-3 is a regulator of pancreatic beta cell replication and • CI-994 is a novel antitumor agent and had activity against survival, and the GSK3 inhibitor CHIR99021 increased the rate of 8 solid tumors tested including pancreatic ductal adenocarcinoma INS-1E beta cell replication. Mussmann, R. et al., “Inhibition of #02, pancreatic adenocarcinoma #03, colon adenocarcinoma GSK3 promotes replication and survival of pancreatic beta cells.” #38, colon adenocarcinoma #51, mammary adenocarcinoma J. Biol. Chem. 282: 12030‑12037 (2007). #25, mammary adenocarcinoma #17/ADR, Dunning • Sold for laboratory or manufacturing purposes only; not for osteogenic sarcoma and the human prostate carcinoma LNCaP. human, veterinary, food, or household use. LoRusso, P.M. et al., “Preclinical antitumor activity of CI-994.” Invest. New Drugs 14: 349‑356 (1996). • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • CI-994 inhibited the growth of two non-small cell lung cancer Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent (NSCLC) cell lines, A-549 (adenocarcinoma) and LX-1 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. (squamous cell carcinoma), with an IC50 of 80 µM. It also showed Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) synergism with standard anticancer agents such as gemcitabine and other common law exemptions of Canadian patent law; (vi) and docetaxel. Loprevite M. et al., “In vitro study of CI-994, a Section 68B of the Patents Act of 1953 in New Zealand together histone deacetylase inhibitor, in non-small cell lung cancer cell with the amendment of same by the Statutes Amendment Bill of lines.” Oncol. Res. 15: 39-48 (2005). 2002; (vii) such related legislation and/or case law as may be or • Sold for laboratory or manufacturing purposes only; not for become applicable in the aforementioned countries; and (viii) such human, medical, veterinary, food, or household use. similar laws and rules as may apply in various other countries. • This product is offered for R&D use in accordance with (i) 35 • Not available in some countries; not available to some institutions; USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese not available for some uses. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. N Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Cl Cl N NH H Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of N N 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such N N CH similar laws and rules as may apply in various other countries. 3 N • Not available in some countries; not available to some institutions; H not available for some uses.

4-(3'-Chloroanilino)-6,7-dimethoxyquinazoline — see H Tyrphostin AG 1478 (Cat. No. T-7310 on page 118). Me N H NH CI-940 — see Leptomycin B (Cat. No. L-6100 on page 63). 2 O N

O

CI-1040 — see PD 184352, FreeC-2606 Base (Cat. No. P-8499 on page 83).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAC-2606GE iv 2010-02-12 FOR DISPOSAL HZ_RevSKC.skc CODE EXPLANATIONS 21 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

is currently approved in at least one country for use in children CI-1033 — see Canertinib, Dihydrochloride Salt (Cat. No. C-1201 on page 17). with relapsed or refractory acute lymphoblastic leukemia (ALL). THE CLOFARABINE, FREE BASE RESEARCH COMPOUND Ciclosporin A — see Cyclosporin A (Cat. No. C-6000 on page 25). SOLD BY LC LABORATORIES IS NOT CLOLAR® NOR EVOLTRA® AND IS NOT FOR HUMAN USE. CIP 18770 – see Delanzomib, Free Base (Cat. No. D-4011 on page 28). • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. CL-1957A — see Leptomycin B (Cat. No. L-6100 on page 63). • This product is offered for R&D use in accordance with (i) 35 Cl-F-Ara-A — see Clofarabine, Free Base USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese (Cat. No. C-1999 on page 22). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. C-1999 Clofarabine, Free Base, >99% Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Synonyms: [CAFdA] [CHEBI:120185] [Cl-F-Ara-A] and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Related Terms: [Clofarex] [Clolar] [Evoltra] with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or Size US$ ¤ £ ¥ become applicable in the aforementioned countries; and (viii) such 50 mg 37 28 24 3,500 similar laws and rules as may apply in various other countries. 100 mg 49 38 32 4,600 • Not available in some countries; not available to some institutions; 200 mg 75 58 49 7,100 not available for some uses. 250 mg 89 69 58 8,400 NH 500 mg 171 132 112 16,200 2 N 1 g 285 219 187 26,900 N 2 g 498 383 327 47,100 Cl N N NOTE: Euro, Pound and Yen prices are revised regularly. HO Please visit www.LCLabs.com for our current prices. O F M.W. 303.68 c10H11ClFN5O3 [123318-82-1 M.I. 14: 2372 OH Storage: Store at or below -20 ºC. Solubility: Soluble Clofarex — see its active ingredient, namely Clofarabine, Free Base in DMSO at 150 mg/mL; soluble in ethanol at 2.8 mg/ (Cat. No. C-1999 on page 22). mL with warming; soluble in water at 2.5 mg/mL with warming; buffers, serum, or other additives may increase Clolar — see its active ingredient, namely Clofarabine, Free Base or decrease the aqueous solubility. Disposal: A (Cat. No. C-1999 on page 22). • Clofarabine is a second generation purine nucleoside analogue. CNF2024 — see BIIB021, Free Base (Cat. No. B-7100 on page 10). • Clofarabine has multiple properties including inhibition of Cocarcinogen A1 — see Phorbol 12-Myristate 13-Acetate ribonucleotide reductase, incorporation into DNA, and induction (Cat. No. P-1680 on page 87). of apoptosis. Kantarjian, H.M. et al., “Clofarabine: past, present, and future.” Leuk. Lymphoma. 48: 1922‑1930 (2007). Colforsin — see Forskolin (Cat. No. F-9929 on page 44). • When clofarabine was used in 42 pediatric patients with Compound C — see Dorsomorphin, Free Base multiply relapsed or refractory acute myeloid leukemia (AML), (Cat. No. D‑3197 on page 30) and Dorsomorphin, the response rate was 26%, including one complete response Dihydrochloride Salt (Cat. No. D‑3456 on page 31). without platelet recovery and 10 partial responses. Jeha, S. et al., “Phase II study of clofarabine in pediatric patients with CP-358774 — see Erlotinib, Free Base (Cat. No. E-4997 on page 37) and Erlotinib, Hydrochloride Salt (Cat. No. E-4007 on page 38). refractory or relapsed acute myeloid leukemia.” J. Clin. Oncol. 27: 4392‑4397 (2009). CP-690550 — see Tofacitinib, Free Base (Cat. No. T‑1377 on page 114) • Clofarabine may be used in patients age 60 years or older with and Tofacitinib, Citrate Salt (Cat. No. T‑1399 on page 115). untreated AML who have at least one unfavorable prognostic CP-690550 Citrate — see Tofacitinib, Citrate Salt factor. Kantarjian, H.M. et al., “Phase II Study of Clofarabine (Cat. No. T‑1399 on page 115). Monotherapy in Previously Untreated Older Adults With Acute Myeloid Leukemia and Unfavorable Prognostic Factors.” CPB — see Alvocidib, Free Base (Cat. No. A-3465 on page 6). J. Clin. Oncol. 28: 549‑555 (2010). CPT-11 — see Irinotecan, Hydrochloride Salt, Trihydrate • Combination treatment of HCT-116, K562, HL-60, or RL tumors (Cat. No. I-4122 on page 57). with clofarabine and 1-β-D-[4-thio-arabinofuranosyl]-cytosine (T-AraC) had dramatically superior anti-tumor activity than treatment with either agent alone, but this combination caused antagonism in CCRF-CEM tumors. The antitumor activity of clofarabine plus T-AraC against HCT-116 tumors in vivo was much better than the activity observed with clofarabine plus 1-β-D-arabinofuranosyl cytosine (AraC). Parker, W.B. et al., “Enhancement of the in vivo antitumor activity of clofarabine by 1-β-D-[4-thio-arabinofuranosyl]-cytosine.” Cancer Chemother. Pharmacol. 64: 253‑261 (2009). • Clofarabine is a powerful radiosensitizer by interfering with the DNA damage response in vitro and in vivo. Cariveau, M.J. et al., “Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA damage response.” Int. J. Radiat. Oncol. Biol. Phys. 70: 213‑220 (2008). • Clofarabine is the active ingredient in the drug product sold under the trade name Clolar® in the U.S. and Canada, and under the trade name Evoltra® in Europe and Australia/New Zealand. This drug

22 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

was 64% and the disease control rate was 90%. Gastrointestinal C-7900 Crizotinib, Free Base, >99% toxicities (nausea and vomiting) were the most frequent adverse Synonyms: [PF-02341066] [PF-1066] [PF-2341066] events. Bang, Y. et al., “Clinical activity of the oral ALK inhibitor Related Terms: [Xalkori] PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). Size US$ ¤ £ ¥ • Crizotinib is the active ingredient in the drug sold under the trade 5 mg 33 24 21 3,200 name Xalkori®. This drug is currently approved in at least one Prices 10 mg 47 35 29 4,600 country for use in patients with certain late-stage (locally advanced Reduced! 25 mg 109 80 68 10,600 or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE 50 mg 158 117 99 15,400 CRIZOTINIB, FREE BASE RESEARCH COMPOUND SOLD 100 mg 252 186 157 24,600 BY LC LABORATORIES IS NOT XALKORI® AND IS NOT 200 mg 397 293 248 38,700 FOR HUMAN USE. 500 mg 730 538 456 71,200 • This crizotinib product is the free base, whose CAS number is 1 g 1100 819 693 108,200 given above. The CAS number of the acetate salt is 877399-53-6. 2 g 1688 1245 1054 164,500 • Another CAS number previously assigned to crizotinib, namely NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 912279-98-2, has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for M.W. 450.34 c H Cl FN O [877399-52-5] 21 22 2 5 human, veterinary, food, or household use. Storage: Store at or below -20 ºC. Solubility: Soluble • This product is offered for R&D use in accordance with (i) 35 in DMSO at 25 mg/mL with warming; soluble in ethanol USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese at 25 mg/mL with warming; very poorly soluble in water; Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent maximum solubility in plain water is estimated to be about Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 10-20 µM; buffers, serum, or other additives may increase Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) or decrease the aqueous solubility. Disposal: A and other common law exemptions of Canadian patent law; (vi) • Crizotinib, also known as PF-02341066, is a potent ATP- Section 68B of the Patents Act of 1953 in New Zealand together competitive, recombinant human c-Met kinase inhibitor with the amendment of same by the Statutes Amendment Bill of (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte 2002; (vii) such related legislation and/or case law as may be or growth factor (HGF)-stimulated or constitutive total tyrosine become applicable in the aforementioned countries; and (viii) such phosphorylation of wild-type c-Met in a panel of human tumor similar laws and rules as may apply in various other countries. and endothelial cell lines. It showed activity against c-Met • Not available in some countries; not available to some institutions; phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK not available for some uses. canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC = 9.7 nM), induced H 50 N apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF- stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC of 11 and 6.1 nM, respectively), and inhibited 50s N N MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) Cl CH in human umbilical vascular endothelial cells. In addition, 3 it inhibited serum-stimulated human dermal microvascular N endothelial cell branching tubulogenesis (formation of vascular O NH tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo 2 in c-Met-dependent human xenograft models including GTL- Cl 16 human gastric carcinoma, U87MG human glioblastoma, F NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. CsA – see Cyclosporin A (Cat. No. C-6000 on page 25). Zou, H.Y. et al., “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy CSF-1 Receptor Inhibitor – see GW2580, Free Base through antiproliferative and antiangiogenic mechanisms.” (Cat. No. G-5903 on page 51). Cancer Res. 67: 4408‑4417 (2007). CT-47098 – see Delanzomib, Free Base • The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation (Cat. No. D-4011 on page 28). in athymic mice bearing GTL16 tumors corresponded to the CT53518 – see Tandutinib, Free Base (Cat. No. T-7802 on page 110). EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation CT99021 – see CHIR99021, Free Base (>90%) is required to significantly inhibit tumor growth (>50%). (Cat. No. C-6556 on page 20). Yamazaki, S. et al., “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267‑1274 (2008). • Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z. et al., “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296‑306 (2010). • 76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 23 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

become applicable in the aforementioned countries; and (viii) such C-8460 CUDC-101, Free Base, >99% similar laws and rules as may apply in various other countries. Size US$ ¤ £ ¥ • Not available in some countries; not available to some institutions; 5 mg 59 45 36 4,900 not available for some uses. 10 mg 87 66 54 7,300

25 mg 167 127 103 13,900 H 50 mg 319 242 197 26,600 H N 100 mg 577 438 357 48,200 N O HO N 200 mg 962 731 595 80,300 O H C 3 NOTE: Euro, Pound and Yen prices are revised regularly. O N Please visit www.LCLabs.com for our current prices. Cyanein – see Brefeldin A (Cat. No. B-8500 on page 14). M.W. 434.49 c24H26N4O4 [1012054-59-9] Storage: Store at or below -20 ºC. CYC202 – see Roscovitine (Cat. No. R-1234 on page 99). Solubility: Soluble in DMSO at 28 mg/mL; very C-8700 Cyclopamine, Free Base, >99% poorly soluble in ethanol; very poorly soluble [11-Deoxyjervine] in water; maximum solubility in plain water is estimated to be about 20-50 µM; buffers, serum, Size US$ ¤ £ ¥ or other additives may increase or decrease the 10 mg 66 48 39 7,600 aqueous solubility. Disposal: A Prices 25 mg 84 61 50 9,700 Reduced! • CUDC-101 is a potent inhibitor of histone deacetylase (HDAC) 50 mg 152 111 90 17,500 and the receptor kinases epidermal growth factor receptor (EGFR) 100 mg 237 173 141 27,300 and human epidermal growth factor receptor 2 (HER2), with 300 mg 618 451 367 71,300 IC50 values of 4.4, 2.4, and 15.7 nM, respectively. It inhibted 500 mg 675 493 401 77,800 EGFR and Her2 phosphorylation, reduced cell proliferation 1 g 1190 869 708 137,200 and induced apoptosis in HCC827 non-small cell lung cancer 2 g 2175 1588 1293 250,800 (NSCLC) xenografts. CUDC-101 inhibited EGFR and induced NOTE: Euro, Pound and Yen prices are revised regularly. upregulation of acetylated histone H3 in a dose-dependent fashion. Please visit www.LCLabs.com for our current prices. CUDC-101 is efficacious in EGFR inhibitor sensitive and resistant M.W. 411.62 c H NO [4449-51-8] NSCLC cell lines and xenografts. CUDC-101 is also efficacious 27 41 2 in epidermoid, pancreatic, and hepatocellular cancer cell lines M.I. 14: 10201 and xenografts. Bao, R. et al., “Potent Anti-Cancer Activity In SPECIAL HAZARD: TERATOGEN. Gloves and mask Vitro and In Vivo by a Novel, Small Molecule Inhibitor of HDAC, should be worn when using this compound. Care must be EGFR and Her2.” http://www.curis.com/images/pipline_pdf/ taken to prevent contact through all routes of exposure. CurisCHIPoster2007Oct16.pdf. Women of childbearing age should be extremely careful in • CUDC-101 inhibted histone deacetylase and synergistically handling cyclopamine! blocked key regulators of EGFR/HER2 signaling pathways. It Storage: Store at or below -20 ºC. Solubility: See Below. also attenuated multiple compensatory pathways including AKT, Disposal: A HER3, and MET, which enable cancer cells to escape the effects • Cyclopamine blocks activation of the Hedgehog response pathway of conventional EGFR/HER2 inhibitors. CUDC-101 might associated with mutations that either activate the proto-oncogene improve the treatment of tumors that cannot be controlled with Smoothened (Smo) or inactivate the tumour suppressor Patched single-target agents. Lai, C.J. et al., “CUDC-101, a multitargeted (Ptch) both of which encode multipass transmembrane proteins. inhibitor of histone deacetylase, epidermal growth factor receptor, Furthermore, it has been demonstrated that the inhibitory effect of and human epidermal growth factor receptor 2, exerts potent cyclopamine results from its direct binding to the Smo heptahelical anticancer activity.” Cancer Res. 70: 3647‑3656 (2010). protein bundle.Taipale, J. et al.” Effects of oncogenic mutations in • CUDC-101 inhibited the proliferation of most tumor cell Smoothened and Patched can be reversed by cyclopamine.” Nature lines tested with greater potency than vorinostat (SAHA), 406: 944-945 (2000). Chen, J.K. et al.” Inhibition of Hedgehog erlotinib, lapatinib, and combinations of vorinostat/erlotinib signaling by direct binding of cyclopamine to Smoothened.” Genes and vorinostat/lapatinib. In vivo, CUDC-101 promoted tumor & Dev. 16: 2743-2748 (2002) regression in various cancer xenograft models such as non- • Induces chick embryo malformations associated with the small cell lung cancer (NSCLC), liver, breast, head and neck, interruption of Sonic hedgehog (Shh)-mediated dorsoventral colon, and pancreatic cancers. Cai, X. et al., “Discovery of patterning. Incardona, J.P. et al.” The teratogenic Veratrum 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)- alkaloid cyclopamine inhibits sonic hedgehog signal transduction.” N-hydroxyheptanamide (CUDC-101) as a potent multi-acting Development. 125: 3553-3562 (1998). HDAC, EGFR, and HER2 inhibitor for the treatment of cancer.” J. Med. Chem. 53: 2000‑2009 (2010). • Displays anti-tumor properties. It has been shown to induce apoptosis in both colorectal adenoma- and carcinoma-derived • Our CUDC-101 product is the free base, whose CAS number cell lines and in skin basal cell carcinomas. Qualtrough, D. et al.” is given above. The CAS number of the hydrochloride salt is Hedgehog signalling in colorectal tumour cells: induction of 1133147-76-8. apoptosis with cyclopamine treatment.” Int J Cancer. 110: 831- • Sold for laboratory or manufacturing purposes only; not for 837 (2004). Tabs, S. and Avci, O.” Induction of the differentiation human, veterinary, food, or household use. and apoptosis of tumor cells in vivo with efficiency and • This product is offered for R&D use in accordance with (i) 35 selectivity.” Eur J Dermatol. 14: 96-102 (2004). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Pregnant cattle, goats, or sheep who graze on the corn lily plant Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Veratrum californicum at the 14th day of gestation (for sheep) can Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. give birth to deformed offspring with a characteristic single eye in Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) the middle of the forehead. [For example, view www.cybergoat. and other common law exemptions of Canadian patent law; (vi) com/cyclopia/cyclopia.htm] Section 68B of the Patents Act of 1953 in New Zealand together This type of birth defect recalls one of the most unforgettable with the amendment of same by the Statutes Amendment Bill of images in all of mythology, namely Homer’s Cyclops (for which 2002; (vii) such related legislation and/or case law as may be or cyclopamine was named). If plants containing cyclopamine or a

24 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

similar compound existed in the Mediterranean area in ancient (Ki = 270 nM). Etzkorn, F.A. et al., “Cyclophilin residues that times, it would then seem likely that the Cyclops was not merely affect noncompetitive inhibition of the protein serine phosphatase a product of Homer’s imagination but rather was based on known, activity of calcineurin by the cyclophilin-cyclosporin A complex.” naturally-occurring birth defects in animals. Alternatively, this Biochemistry 33: 2380‑2388 (1994). Liu, J., “FK-506 and type of birth defect might arise from spontaneous mutation, as ciclosporin: molecular probes for studying intracellular signal may have been the case for the kitten recently reported: www. transduction.” Trends Pharmacol. Sci. 14: 182‑188 (1993). samtsai.com/p131. • Inhibits interleukin-1α-, lipopolysaccharide-, and TNF-α- • CYCLOPAMINE SOLUBILITY: Ethanol is the best cyclopamine nitric oxide synthesis induction. Fast, D.J. et al., “Cyclosporin solvent for biological use. A 2% solution (20 mg/mL) can be A inhibits nitric oxide production by L929 cells in prepared by warming the cyclopamine in ethanol to 50‑60 °C; response to tumor necrosis factor and interferon-gamma.” boiling is not necessary. Upon cooling, the cyclopamine J. Interferon Res. 13: 235‑240 (1993). Marumo, T. et al., remains in solution at room temperature, even if left for several “Cyclosporin A inhibits nitric oxide synthase induction in days. However, storage at -20 ºC is recommended, and at this vascular smooth muscle cells.” Hypertension 25: 764‑768 (1995). temperature the cyclopamine will crystallize out of solution. Upon Hattori, Y. and Naranishi, N., “Effects of cyclosporin A and thawing, the mixture will need to be heated again to redissolve the FK-506 on nitric oxide and tetrahydrobiopterin synthesis cyclopamine. in bacterial lipopolysaccharide-treated J774 macrophages.” Methanol and DMSO can also be used as cyclopamine solvents, Cell Immunol. 165: 7‑11 (1995). but solubility in methanol is only about 0.7% (7 mg/mL) at best, • See also our other standard immunosuppresent products: and solubility in DMSO is about 0.4% (4 mg/mL). Substantial - Rapamycin (Cat. No. R-5000 on page 96) heating is again needed to achieve solution with methanol or - FK-506 (Cat. No. F-4900 on page 42) DMSO, but once the cyclopamine is dissolved it will remain in solution if kept at room temperature. Storage in either solvent at • Cyclosporin A is the active ingredient in the drugs sold under the ® ® the recommended -20 ºC will also cause crystallization, as noted trade names Neoral or Sandimune . NOTE: the cyclosporin A ® ® above for ethanol, and reheating is necessary after thawing in sold by LC Laboratories is NOT Neoral nor Sandimune and is order to achieve full dissolution. NOT for human use. Methanol is less desirable than the other two solvents because it • Sold for laboratory or manufacturing purposes only; not for is the most volatile; merely standing open in air will lead to slow human, veterinary, food or household use.

volume loss and consequent artefactual increase in concentration H C of the solution. DMSO is the least volatile solvent and is preferred 3 if a stock solution need only be 4 mg/mL or less. Ethanol is a CH compromise between volatility and achievable concentration. 3 HO H C CH O CH O • Sold for laboratory or manufacturing purposes only; not for 3 3 3 human, veterinary, food,or household use. H C N NH CH 3 3 N N N NH CH O CH O O 3 3 H C CH 3 3 H C H C CH 3 3 3

O H C CH CH N CH 3 3 3 3 CH 3 O H C CH O 3 O CH 3 3 N NH NH H C NH N CH HO 3 3 O CH O CH O C-6000 Cyclosporin A, >99% 3 3 HCC H [Antibiotic S 7481F1] [Ciclosporin A] [CsA] 3 3 [Cyclosporine] [Neoral] [Ramihyphin A] [Sandimune] Cyclosporine — see Cyclosporin A (Cat. No. C-6000 on page 25). Size US$ ¤ £ ¥ D04014 — see Enzastaurin, Free Base (Cat. No. E-4506 on page 34). 1 g 48 35 30 3,700 DAC — see Decitabine, Free Base (Cat. No. D-3899 on page 27). 5 g 165 120 104 12,700 10 g 295 214 187 22,700 Dacogen — see its active ingredient, namely Decitabine, Free Base 25 g 575 416 364 44,200 (Cat. No. D-3899 on page 27). 100 g 1100 797 696 84,500 Dacplat — see Oxaliplatin (Cat. No. O-7111 on page 79). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Dactolisib — see NVP-BEZ235, Free Base (Cat. No. N-4288 on page 75). M.W. 1202.61 c62H111N11O12 [59865-13-3] M.I. 14: 2752 Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 200 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A • Cyclic hydrophobic oligopeptide isolated from the filamentous fungi, Tolypocladium inflatum, with potent immunosuppressant properties. “Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2.” Proc. Natl. Acad. Sci. USA 91: 7350‑7354 (1994). • The complex of cyclosporin A with the protein cyclophilin inhibits T-cell receptor signal transduction pathway via the inhibition of calcineurin (protein phosphatase 2B) with nanomolar affinity

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 25 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

D-2946 Daidzein, >99% D-7878 Daidzin, >99% [4',7-Dihydroxyisoflavone] [4',7-Dihydroxyisoflavone, 7-O-β-d-glucopyranoside] Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 1 g 33 25 20 2,800 25 mg 37 29 24 4,100 5 g 116 88 72 9,700 50 mg 48 37 32 5,400 10 g 218 166 135 18,200 100 mg 86 66 57 9,600 25 g 450 342 278 37,600 300 mg 144 111 95 16,100 100 g 1330 1011 823 111,100 500 mg 196 152 130 21,900 NOTE: Euro, Pound and Yen prices are revised regularly. 1 g 278 215 184 31,100 Please visit www.LCLabs.com for our current prices. 2 g 482 373 319 53,900 M.W. 254.24 c15H10O4 [486-66-8] 5 g 995 769 658 111,200 M.I. 14: 2801 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 200 mg/mL; very poorly soluble in ethanol; very M.W. 416.38 c21H20O9 [552-66-9] poorly soluble in water; maximum solubility in plain water M.I. 14: 2801 is estimated to be about 50-100 µM; buffers, serum, or Storage: Store at or below -20 °C. other additives may increase or decrease the aqueous Solubility: Soluble in DMSO at 100 mg/mL; soluble in solubility. Disposal: A ethanol at 10 mg/mL with warming; very poorly soluble in • Negative control for genistein. Akiyama, T. et al., water; maximum solubility in plain water is estimated to be J. Biol. Chem. 262: 5592‑5595 (1987). Wijetunge, S. et al., about 100‑200 µM; buffers, serum, or other additives may Biochem. Biophys. Res. Comm. 189: 1620‑1623 (1992). increase or decrease the aqueous solubility. Disposal: A • Please request Technical Note #22 for additional information. • Isoflavone derivative found in soy-based food products. Wang, H. • Daidzein is also a cytostatic agent capable of arresting the cell and Murphy, P.A., “Isoflavone content in commercial soybean foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). cycle at G1. • Weak inhibitor of hamster mitochondrial alcohol • See the extensive comments before the listing for Genistein dehydrogenase. Keung, W.M., Klyosov, A.A. and Vallee, B.L. (Cat. No. G-6055 on page 48). Proc. Natl. Acad. Sci. USA 94: 1675‑1679 (1997). • Inhibits ethanol intake of Syrian golden hamsters and rats, and • Isoflavone derivative found in soy-based food products. Wang, H. inhibits human mitochondrial alcohol dehydrogenase (ADH) but and Murphy, P.A., “Isoflavone content in commercial soybean not hamster cytosolic ADH; further evidence suggests that the foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). mechanism for reducing alcohol consumption is different from • See the extensive comments before the listing for Genistein ADH inhibition typical of antabuse-type drugs. Keung, W.M. (Cat. No. G-6055 on page 48). et al., Proc. Natl. Acad. Sci. USA 94: 1675‑1679 (1997). • See also these related products: • See also these related products: - 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). - 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). - Daidzin (Cat. No. D-7878 on page 26). - Daidzein (Cat. No. D-2946 on page 26). - (R,S)-Equol (Cat. No. E-5880 on page 37). - 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). - 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. OH O OH O OH

O O O

HO O OH HO HO

Daidzin 6''-O-Acetate — see 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). Daidzin 6''-O-Malonate — see 6"-O-Malonyldaidzin, Free Acid (Cat. No. M-6730 on page 67).

26 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

2002; (vii) such related legislation and/or case law as may be or D-3307 Dasatinib, Free Base, >99% become applicable in the aforementioned countries; and (viii) such [BMS-354825] [Sprycel] similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; Size US$ ¤ £ ¥ not available for some uses. 500 mg 47 38 30 3,700 1 g 62 47 39 5,100 2 g 114 87 72 9,300 N N N 5 g 194 148 122 15,800 NH 10 g 305 233 192 24,900 S NH N O N 25 g 725 553 457 59,200 Cl OH NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. DB03496 — see Alvocidib, Free Base (Cat. No. A-3465 on page 6). M.W. 488.01 c H ClN O S [302962-49-8] 22 26 7 2 D-3899 Decitabine, Free Base, >99% Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 200 mg/mL; very poorly soluble in ethanol; very Synonyms: [5-Aza-dC] [5-Aza-2'-deoxycytidine] poorly soluble in water; maximum solubility in plain water [DAC] [Dezocitidine] is estimated to be about 10 µM; buffers, serum, or other Related Terms: [Dacogen] additives may increase or decrease the aqueous solubility. Disposal: A Size US$ ¤ £ ¥ • Small molecule inhibitor of both the SRC and BCR/ABL 50 mg 69 50 41 7,800 tyrosine kinases with IC50’s for the isolated kinases of 0.55 New! 100 mg 91 65 55 10,300 and 3.0 nM, respectively. Lombardo, LJ et al., “Discovery 200 mg 136 98 82 15,400 of N-(2-chloro-6-methylphneyl)-2-(6-(4-(2-hydroxyethyl)- 250 mg 155 111 93 17,600 piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5- 500 mg 222 160 133 25,200 carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor 1 g 366 263 220 41,600 with potent antitumor activity in pre-clinical assays.” J. Med. Chem. 47: 6658‑6661 (2004). 2 g 578 416 347 65,700 5 g 925 665 556 105,100 • Dasatinib also inhibits Lyn (IC = 8.5 nM) and Src (IC = 3.0 50 50 NOTE: Euro, Pound and Yen prices are revised regularly. nM) kinase activities in vitro using 0.1 mg/mL poly (Glu4-Tyr) Please visit www.LCLabs.com for our current prices. as the substrate. Nam, S. et al., “Action of the Src Family Kinase Inhibitor, Dasatinib (BMS-354825), on Human Prostate Cancer M.W. 228.21 c8H12N4O4 [2353-33-5] Cells.” Cancer Res. 65: 9185‑9189 (2005). M.I. 15: 2586 • Dasatinib exhibits greater potency than imatinib mesylate and Storage: Store at or below -20 ºC. Solubility: Soluble in inhibits the majority of kinase mutations in imatinib-resistant DMSO at 90 mg/mL; soluble in ethanol at 2 mg/mL with chronic myeloid leukemia. Copland, M. et al., “Dasatinib (BMS- warming; soluble in water at 25 mg/mL with warming; 354825) targets an earlier progenitor population than imatinib buffers, serum, or other additives may increase or in primary CML but does not eliminate the quiescent fraction.” decrease the aqueous solubility. Disposal: A Blood 107: 4532‑4539 (2006). • Decitabine is a cytosine nucleoside analog and inhibits • Responses were seen in patients with all BCR/ABL genotypes, further DNA methylation after incorporated into DNA. As with the exception of T315I mutation, which confers resistance to a consequence, tumor suppressor genes aberrantly silenced both dasatinib and imatinib in vitro. O’Hare, T. et al., after methylation can be reactivated and expressed. Decitabine “In vitro Activity of Bcr-Abl Inhibitors AMN107 and BMS- has shown activity in some hematologic disorders including 354825 against Clinically Relevant Imatinib-Resistant Abl Kinase myelodysplastic syndromes (MDS), acute myelogenous Domain Mutants.” Cancer Res. 65: 4500‑4505 (2005). leukemia (AML) and chronic myelogenous leukemia (CML). Leone, G. et al., "DNA methylation and demethylating drugs • Dasatinib and nilotinib are respectively 325-fold (IC50: 0.6 versus in myelodysplastic syndromes and secondary leukemias." 280 nM) and 20-fold (IC50: 15 versus 280 nM) more potent than imatinib against cells expressing wild-type Bcr-Abl. Similar Haematologica 87: 1324‑1341 (2002). improvements are maintained for all imatinib-resistant mutants • Treatment of patients with sickle cell disease (SSD) with tested, with the exception of T315I. Thus, both inhibitors hold subcutaneous decitabine increased fetal hemoglobin (HbF) levels promise for treating imatinib-refractory CML. O’Hare, T. et al., and improved SSD pathophysiology such as red cell adhesion, “In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 endothelial damage, and coagulation pathway activity without against clinically relevant imatinib-resistant Abl kinase domain cytotoxicity. Saunthararajah, Y. et al., "Effects of 5-aza-2'- mutants.” Cancer Res. 65: 4500‑4505 (2005). deoxycytidine on fetal hemoglobin levels, red cell adhesion, and • Dasatinib is the active ingredient in the drug sold under the trade hematopoietic differentiation in patients with sickle cell disease." name Sprycel®. The drug is currently approved in at least one Blood 102: 3865‑3870 (2003). country for use in patients with chronic myelogenous leukemia • A phase III study demonstrated that decitabine was clinically and Philadelphia chromosome-positive acute lymphoblastic effective in the treatment of patients with MDS. Decitabine leukemia. It is also being assessed for use in metastatic melanoma. showed durable responses and delayed time to AML NOTE: the dasatinib sold by LC Laboratories is NOT Sprycel® transformation/death. Kantarjian, H. et al., "Decitabine improves and is NOT for human use. patient outcomes in myelodysplastic syndromes: results of a phase • Sold for laboratory or manufacturing purposes only; not for III randomized study." Cancer 106: 1794‑1803 (2006). human, medical, veterinary, food, or household use. • Decitabine is the active ingredient in the drug sold under the • This product is offered for R&D use in accordance with (i) 35 trade name Dacogen®. This drug is currently approved in at USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese least one country for use in patients with MDS. NOTE: THE Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent DECITABINE FREE BASE RESEARCH COMPOUND SOLD Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. BY LC LABORATORIES IS NOT DACOGEN® AND IS NOT Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) FOR HUMAN USE. and other common law exemptions of Canadian patent law; (vi) • Other CAS numbers previously assigned to Decitabine, Free Base, Section 68B of the Patents Act of 1953 in New Zealand together namely 105597-46-4 and 123795-43-7, have been deleted by CAS with the amendment of same by the Statutes Amendment Bill of and are no longer in use.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 27 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Sold for laboratory or manufacturing purposes only; not for and glomerulonephritis in two preclinical mouse models of SLE." human, veterinary, food, or household use. Int. Immunopharmacol. 12: 257‑270 (2012). • This product is offered for R&D use in accordance with (i) 35 • As of this writing (October 2013), the structure for delanzomib USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese shown on the SelleckChem.com website is not correct. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Sold for laboratory or manufacturing purposes only; not for Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. human, veterinary, food, or household use. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • This product is offered for R&D use in accordance with (i) 35 and other common law exemptions of Canadian patent law; (vi) USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Section 68B of the Patents Act of 1953 in New Zealand together Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent with the amendment of same by the Statutes Amendment Bill of Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 2002; (vii) such related legislation and/or case law as may be or Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) become applicable in the aforementioned countries; and (viii) such and other common law exemptions of Canadian patent law; (vi) similar laws and rules as may apply in various other countries. Section 68B of the Patents Act of 1953 in New Zealand together • Not available in some countries; not available to some institutions; with the amendment of same by the Statutes Amendment Bill of not available for some uses. 2002; (vii) such related legislation and/or case law as may be or NH 2 become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. N N • Not available in some countries; not available to some institutions; HO N O not available for some uses. O HO CH 3 O OH H OH N N B N OH H Decumbin — see Brefeldin A (Cat. No. B-8500 on page 14). O CH 3

Deforolimus — see Ridaforolimus (Cat. No. R-7040 on page 97). CH 3 D-4011 Delanzomib, Free Base, >99% 11-Deoxyjervine — see Cyclopamine (Cat. No. C-8700 on page 24). Synonyms: [CEP-18770] [CIP 18770] [CT-47098] [NPH007098] 12-Deoxyphorbol 13-Acetate — see Prostratin (Cat. No. P-4462 on page 94). Size US$ ¤ £ ¥ Dezocitidine — see Decitabine, Free Base 1 mg 79 57 47 9,000 (Cat. No. D‑3899 on page 27). New! 5 mg 188 135 113 21,400 dFdC — see Gemcitabine, Free Base (Cat. No. G‑4199 on page 46) 10 mg 246 177 148 27,900 and Gemcitabine, Hydrochloride Salt 25 mg 489 352 294 55,600 (Cat. No. G‑4177 on page 46). 50 mg 685 492 411 77,800 dFdCyd — see Gemcitabine, Free Base (Cat. No. G-4199 on page 46). 100 mg 1140 820 685 129,500 200 mg 1825 1312 1096 207,300 4',7-Dihydroxy-6-methoxyisoflavone — see Glycitein NOTE: Euro, Pound and Yen prices are revised regularly. (Cat. No. G-1152 on page 49). Please visit www.LCLabs.com for our current prices. 4',7-Dihydroxyisoflavone — see Daidzein M.W. 413.28 c21H28BN3O5 [847499-27-8] (Cat. No. D-2946 on page 26). : Store at or below -20 ºC. : Soluble in Storage Solubility 4',7-Dihydroxyisoflavone, 7-O-b-d-glucopyranoside — see Daidzin DMSO. Disposal: A (Cat. No. D-7878 on page 26). • Delanzomib, also known as CEP-18770, is proteasome inhibitor. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin — see It inhibited chymotrypsin-like proteasome activity with an IC50 17-DMAG (Cat. No. D-3440 on page 28). of 3.8 nM but had marginal inhibition of the tryptic and peptidyl glutamyl activities of the proteosome. It blocked the growth of DJM-166 — see PX-866 (Cat. No. P-7501 on page 94). representative human solid and hematological tumor cell lines DJM-2-166 — see PX-866 (Cat. No. P-7501 on page 94). with IC50 values of <35 nM. It also inhibited endothelial cell survival, proliferation, and morphogenesis. It had a favorable D-3440 17-DMAG, Hydrochloride Salt, >99% tumor selectivity profile for the treatment of multiple myeloma (MM) and other malignancies in vivo. Piva, R. et al., "CEP- [Alvespimycin] [17-(Dimethylaminoethylamino)-17- 18770: A novel, orally active proteasome inhibitor with a tumor- demethoxygeldanamycin] selective pharmacologic profile competitive with bortezomib." Blood 111: 2765-2775 (2008). Size US$ ¤ £ ¥ • Delanzomib in combination with dexamethasone and/or 25 mg 42 31 27 3,300 lenalidomide demonstrated superior tumor growth inhibition and 100 mg 87 65 56 6,800 extended tumor growth delay when compared to vehicle alone, 250 mg 198 148 127 15,500 these drugs alone, or the combination of dexamethasone and 500 mg 262 196 168 20,400 lenalidomide. Sanchez, E. et al., "CEP-18770 (delanzomib) in 1 g 475 354 304 37,100 combination with dexamethasone and lenalidomide inhibits the 2 g 825 616 529 64,400 growth of multiple myeloma." Leuk. Res. 36: 1422‑1427 (2012). 5 g 1468 1096 941 114,600 • Treatment of MRL/lpr lupus mice and NZM lupus nephritis mice 10 g 2150 1605 1378 167,800 with delanzomib reduced the level of circulating proinflammatory NOTE: Euro, Pound and Yen prices are revised regularly. cytokines and disease-promoting antinuclear antibodies. Please visit www.LCLabs.com for our current prices. Delanzomib protected MRL/lpr lupus mice from developing M.W. 653.21 c H N O •HCl [467214-21-7] fatal lupus nephritis and reversed lupus nephritis in NZM mice. 32 48 4 8 Delanzomib treatment extended the survival of mice with lupus Warning: Toxic. nephritis. Seavey, M.M. et al., "Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms

28 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

Storage: Store at or below -20 ºC. Solubility: Soluble in results in apoptosis of human leukemia HL-60 cells arrested at the DMSO; Soluble up to about 2 mg/mL in water. M phase in the cell cycle. Pazdur, R. et al., “The taxoids: paclitaxel Disposal: A (Taxol) and docetaxel (Taxotere).” Cancer Treat Rev. 19: 351-386 • Synthetic derivative of geldanamycin (Cat. No. G-4500 on page 46) (1993). Hagisawa, S. et al., “Docetaxel-induced apoptosis in the and water-soluble analog of 17-AAG (Cat. No. A-6880 on page 1) mitotic phase: electron microscopic and cytochemical studies demonstrating stability and low in vivo toxicity similar to 17-AAG, of human leukemia cells.” Med Electron Microsc. 32: 167-174 but undergoes limited metabolism compared to 17-AAG. Egorin, (1999). M.J. et al., “Pharmacokinetics, tissue distribution, and metabolism • Docetaxel has exhibited significant antitumor activity against of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin prostate cancer, metastatic breast cancer, gastric cancer, and others. (NSC 707545) in CD2F1 mice and Fischer 344 rats.” Cancer Pienta, K.J., “Preclinical mechanisms of action of docetaxel and Chemother. Pharmacol. 49: 7-19 (2002). docetaxel combinations in prostate cancer.” Semin Oncol. 4: 3‑7 • Binds specifically to heat shock protein Hsp90 in a manner (2001). Yoshida, K. et al., “Phase I study of combination therapy similar to geldanamycin. Tian, Z.Q. et al., “Synthesis and with S-1 and docetaxel (TXT) for advanced or recurrent gastric biological activities of novel 17-aminogeldanamycin derivatives.” cancer.” Anticancer Res. 24: 1843‑1851 (2004). Tabernero, J. Bioorg. Med. Chem. 12: 5317-5329 (2004). et al., “A multicentre, randomised phase II study of weekly or 3-weekly docetaxel in patients with metastatic breast cancer.” • Inhibits angiogenesis. Kaur, G et al., “Antiangiogenic properties Ann Oncol. 15: 1358‑1365 (2004). of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator.” • Docetaxel is the active ingredient in the drug sold under the trade ® Clin. Cancer Res. 10: 4813-4821 (2004). name Taxotere . NOTE: the docetaxel sold by LC Laboratories is NOT Taxotere® and is NOT for human use. • Enhances the radiation-induced cell cycle arrest of human solid tumor cell lines both in vitro and in vivo. Bull, • Sold for laboratory or manufacturing purposes only; not for E.E. et al., “Enhanced tumor cell radiosensitivity and human, medical, veterinary, food, or household use. abrogation of G2 and S phase arrest by the Hsp90 inhibitor

17-(dimethylaminoethylamino)-17-demethoxygeldanamycin.” OH Clin. Cancer Res. 10: 8077-8084 (2004). CH O O O H C 3 • Exhibits potent anti-tumor activity against MDA-MB-231 breast 3 OH H C carcinoma cells and HL60-TB leukemia cells both of which are 3 O NH O relatively insensitive to 17-AAG. Hollingshead, M. et al., “In vivo OH antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino- HO O 17-demethoxygeldanamycin hydrochloride), a water-soluble O O O

geldanamycin derivative.” Cancer Chemother. Pharmacol. CH 56: 115‑125 (2005). O 3 • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. O D-2744 Doramapimod, Free Base, >99% NH N O [BIRB 796] •HCl CH 3 NH Size US$ ¤ £ ¥ O 25 mg 78 56 49 6,600 H C 3 H H C O 50 mg 137 99 87 10,600 O 3 H C O CH 3 3 100 mg 185 133 117 14,300 200 mg 330 238 209 25,500 H C 3 500 mg 680 490 430 52,500 OCONH 2 1 g 975 702 616 75,300 NOTE: Euro, Pound and Yen prices are revised regularly. D-1000 Docetaxel, >99% Please visit www.LCLabs.com for our current prices. [RP 56976] [Taxotere] M.W. 527.66 C31H37N5O3 [285983-48-4] Size US$ ¤ £ ¥ Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 50 mg/mL; soluble in ethanol at 30 mg/mL; 100 mg 41 30 25 4,000 very poorly soluble in water; maximum solubility in plain Prices 250 mg 89 64 55 8,700 Reduced! water is estimated to be about 5-20 µM; buffers, serum, 500 mg 149 108 92 14,500 or other additives may increase or decrease the aqueous 1 g 248 180 153 24,200 solubility. Disposal: A 2 g 336 243 208 32,700 • Doramapimod is a protein kinase inhibitor with a >330-fold 5 g 575 417 356 56,000 selectivity for p38 MAPK compared with 12 other protein 10 g 860 623 532 83,800 kinases. In contrast to other p38 MAPK inhibitors (e.g., NOTE: Euro, Pound and Yen prices are revised regularly. SB203580), doramapimod prevents both the kinetic activity and Please visit www.LCLabs.com for our current prices. phosphorylation of p38 MAPK by binding to the ATP pocket as well as to a novel allosteric binding site on p38 MAPK. M.W. 807.88 C43H53NO14 [114977-28-5] M.I. 14: 3397 Branger, J. et al., “Anti-Inflammatory Effects of a p38 Mitogen- Activated Protein Kinase Inhibitor During Human Endotoxemia.” Storage: Store at or below -20 ºC. Solubility: Soluble in J. Immunol. 168: 4070-4077 (2002). DMSO at 200 mg/mL; soluble in ethanol at 100 mg/mL; very poorly soluble in water; maximum solubility in plain • Inhibits ABL(T315I). Doramapimod blocked proliferation of water is estimated to be about 10-20 µM; buffers, serum, cells expressing BCR-ABL(T315I), with an IC50 of 2-3 µM; or other additives may increase or decrease the aqueous this is more potent than for cells expressing BCR-ABL with no solubility. Disposal: A resistance mutation (IC50 > 10 µM). Doramapimod prevented BCR-ABL(T315I) autophosphorylation in Ba/F3 cells (IC50 = 1-2 • Docetaxel, a semisynthetic analog of paclitaxel, shares the latter’s µM). By comparison, imatinib did not inhibit BCR-ABL(T315I) mechanism of action: the promotion of microtubule assembly and in this assay, even at 10 µM. Carter, T.A. et al., “Inhibition of inhibition of microtubule disassembly. This anti-mitotic behavior

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 29 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

drug-resistant mutants of ABL, KIT, and EGF receptor kinases.” Proc. Natl. Acad. Sci. USA 102: 11011-11016 (2005). D-3197 Dorsomorphin, Free Base, >99% • The p38 inhibitor doramapimod binds tightly (Kd = 40 nM) to Synonyms: [AMPK Inhibitor I] [BML-275] ABL(T315I) and inhibits the BMS-354825- and imatinib-resistant [BMP Inhibitor I] [Compound C] ABL(T315I) kinase. Fabian, M.A. et al., “A small molecule-kinase interaction map for clinical kinase inhibitors.” Nat. Biotechnol. Size US$ ¤ £ ¥ 23: 329‑336 (2005). 5 mg 45 32 27 5,100 • Doramapimod has high picomolar affinity (Kd = 100 pM) for New! 10 mg 69 50 41 7,800 25 mg 131 94 79 14,900 p38 MAP kinase and low nanomolar inhibitory activity (IC50 = 18 nM) against TNFα in THP-1 cell culture. The association 50 mg 235 169 141 26,700 of a fluorescent analog of doramapimod to p38 MAP kinase 100 mg 423 304 254 48,100 is slow and the dissociation is even slower. The high overall 250 mg 715 514 430 81,200 binding affinity of doramapimod is due to a reduction in the 300 mg 837 602 503 95,100 dissociation rate constant. The apparent IC value decreases as 50 500 mg 1240 891 745 140,900 the preincubation time increases. The time-dependence of apparent NOTE: Euro, Pound and Yen prices are revised regularly. inhibitory potency and the fluorescent binding assays confirm Please visit www.LCLabs.com for our current prices. the slow binding behavior of doramapimod, which is apparently required for the conformational change of the binding site. M.W. 399.49 c24H25N5O [866405-64-3] Pargellis, C. et al., “Inhibition of p38 MAP kinase by utilizing a Storage: Store at or below -20 ºC. Solubility: Soluble in novel allosteric binding site.” Nat. Struct. Biol. 9: 268-272 (2002). DMSO. Disposal: A • A 600-mg dose of doramapimod in humans strongly inhibited • Dorsomorphin, also known as compound C, is a potent, reversible, LPS-induced coagulation activation, as determined by plasma ATP-competitive AMP-activated protein kinase (AMPK) inhibitor concentrations of the prothrombin fragment F1 + 2. Doramapimod with Ki of 109 nM in the absence of AMP. Zhou, G. et al., "Role of also dose-dependently decreased the activation and subsequent AMP-activated protein kinase in mechanism of metformin action." inhibition of the fibrinolytic system (plasminogen activator J. Clin. Invest. 108: 1167‑1174 (2001). inhibitor type 1, plasma tissue-type plasminogen activator, and • This research compound is the free base form of dorsomorphin. plasmin-α2-antiplasmin complexes) and endothelial cell activation We also offer the dihydrochloride salt form (see Dorsomorphin, (von Willebrand factor and plasma soluble E-selectin). Branger, Dihydrochloride Salt, Cat. No. D-3456 on page 31). J. et al., “Inhibition of coagulation, fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor • Inhibition of bone morphogenetic protein (BMP) signaling by during human endotoxemia.” Blood 101: 4446-4448 (2003). dorsomorphin during the early critical stage of differentiation of pluripotent embryonic stem (ES) cells promoted the development • Doramapimod inhibits the protein kinases p38 and p38 and a β of the cardiomyocyte lineage, but at the expense of reduced is undergoing clinical trials for the treatment of inflammatory differentiation of endothelial, smooth muscle, and hematopoietic diseases. cells. Hao, J. et al., "Dorsomorphin, a selective small molecule • Sold for laboratory or manufacturing purposes only; not for inhibitor of BMP signaling, promotes cardiomyogenesis in human, medical, veterinary, food, or household use. embryonic stem cells." PLoS One 3: e2904 (2008). • This product is offered for R&D use in accordance with (i) 35 • Dorsomorphin disrupted zebrafish angiogenesis, but not USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese by blocking bone morphogenic protein (BMP) signaling. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Dorsomorphin also showed significant "off-target" effects Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. against the vascular endothelial growth factor (VEGF) pathway. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Hao, J. et al., "In vivo structure-activity relationship study of and other common law exemptions of Canadian patent law; (vi) dorsomorphin analogues identifies selective VEGF and BMP Section 68B of the Patents Act of 1953 in New Zealand together inhibitors." ACS. Chem. Biol. 5: 245‑253 (2010). with the amendment of same by the Statutes Amendment Bill of • Dorsomorphin reduced phosphorylation levels of SMAD1/5/8 2002; (vii) such related legislation and/or case law as may be or in cells stimulated by BMP2, BMP4, BMP6, and BMP7 become applicable in the aforementioned countries; and (viii) such selectively, and blocked BMP-, hemojuvelin-, and interleukin similar laws and rules as may apply in various other countries. 6-mediated hepcidin gene transcription and BMP-induced • Not available in some countries; not available to some institutions; osteogenic differentiation. It also inhibited hepcidin transcription not available for some uses. in iron-stimulated zebrafish and induced hyperferremia in iron-replete mice. Yu, P.B. et al., "Dorsomorphin inhibits BMP

O signals required for embryogenesis and iron metabolism." O N Nat. Chem. Biol. 4: 33‑41 (2008). N O N NH NH • The addition of dorsomorphin to the culture medium before treatment with differentiation inducers reduced lipid accumulation in 3T3-L1 cells. Suenaga, M. et al., "BMP Inhibition with dorsomorphin limits adipogenic potential of preadipocytes." J. Vet. Med. Sci. 72: 373‑377 (2010). • Dorsomorphin treatment of MCF7 breast carcinoma cells led to Bax redistribution from the cytoplasm to mitochondria and caused apoptosis at least partly by ceramide upregulation, and probably not by AMPK inhibition. Jin, J. et al., "AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells." J. Lipid Res. 50: 2389‑2397 (2009). • Insulin did not affect glucose transport in control cells but increased glucose uptake for serum-starved cells that was preventable by dorsomorphin. Ching, J.K. et al., "A role for AMPK in increased insulin action after serum starvation." Am. J. Physiol. Cell Physiol. 299: C1171‑C1179 (2010). • Dorsomorphin inhibited the growth of four colorectal cancer cell lines, caused G2/M arrest, and induced apoptotic

30 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

or autophagic death. Yang, W.L. et al., "AMPK inhibitor become applicable in the aforementioned countries; and (viii) such compound C suppresses cell proliferation by induction of similar laws and rules as may apply in various other countries. apoptosis and autophagy in human colorectal cancer cells." • Not available in some countries; not available to some institutions; J. Surg. Oncol. 106: 680‑688 (2012). not available for some uses.

• This dorsomorphin product is the free base form, whose CAS O number is given above. The CAS number of the dihydrochloride N

salt form is 1219168-18-9. N N • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. . 2HCl N • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent N Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) D-3608 Dovitinib, Free Base, >99% and other common law exemptions of Canadian patent law; (vi) [CHIR-258] [TKI-258] Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of Size US$ ¤ £ ¥ 2002; (vii) such related legislation and/or case law as may be or 10 mg 85 65 53 7,100 become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. 25 mg 175 133 108 14,600 50 mg 266 202 165 22,200 • Not available in some countries; not available to some institutions; not available for some uses. 100 mg 445 338 275 37,200 200 mg 790 600 489 66,000 O N 500 mg 1350 1026 835 112,700

N 1 g 2250 1710 1392 187,900 N NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. N M.W. 392.43 c21H21FN6O [405169-16-6] Storage: Store at or below -20 ºC. Solubility: Soluble in N DMSO. Disposal: A • This is the free base form of dovitinib; please see our product D-3456 Dorsomorphin, Dihydrochloride Salt, >99% Dovitinib, Lactate Salt (Cat. No. D-3699 on page 32), for further Synonyms: [AMPK Inhibitor I] [BML-275] technical information. The lactate salt form of dovitinib, not the [BMP Inhibitor I] [Compound C] free base, is used in the dovitinib formulation for biomedical research. Size US$ ¤ £ ¥ • Sold for laboratory or manufacturing purposes only; not for 5 mg 45 32 27 5,100 human, medical, veterinary, food, or household use. New! 10 mg 69 50 41 7,800 • This product is offered for R&D use in accordance with (i) 35 25 mg 131 94 79 14,900 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 50 mg 235 169 141 26,700 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 100 mg 423 304 254 48,100 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 250 mg 715 514 430 81,200 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 300 mg 837 602 503 95,100 and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together 500 mg 1240 891 745 140,900 with the amendment of same by the Statutes Amendment Bill of NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such M.W. 472.41 C24H25N5O•2HCl similar laws and rules as may apply in various other countries. [1219168-18-9] • Not available in some countries; not available to some institutions; Storage: Store at or below -20 ºC. Solubility: Soluble in not available for some uses. DMSO. Disposal: A NH O • This research compound is the dihydrochloride salt form of dorsomorphin; please see the free base form of this product N (Dorsomorphin, Free Base, Cat. No. D-3197 on page 30) for further F NH NH technical information about both of these research compounds. 2 N N • This dorsomorphin product is the dihydrochloride salt, whose CAS number is given above. The CAS number of Dorsomorphin, Free Base form is 866405-64-3. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 31 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Cat. No. D-3608 on page 31, Dovitinib, Free Base. The CAS D-3699 Dovitinib, Lactate Salt, >99% number of dovitinib free base is 405169-16-6. Synonyms: [CHIR-258] [TKI-258] • The CAS number for the monohydrate of dovitinib lactate salt is 915769-50-5. Size US$ ¤ £ ¥ • Another CAS number previously assigned to dovitinib lactate, 10 mg 85 65 53 7,100 namely 1000873-96-0, has been deleted by CAS and is no longer 25 mg 175 133 108 14,600 in use. 50 mg 266 202 165 22,200 • Sold for laboratory or manufacturing purposes only; not for 100 mg 445 338 275 37,200 human, medical, veterinary, food, or household use. 200 mg 790 600 489 66,000 • This product is offered for R&D use in accordance with (i) 35 500 mg 1350 1026 835 112,700 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 1 g 2250 1710 1392 187,900 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent NOTE: Euro, Pound and Yen prices are revised regularly. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Please visit www.LCLabs.com for our current prices. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) M.W. 482.51 c21H21FN6O•C3H6O3 [692737-80-7] and other common law exemptions of Canadian patent law; (vi) Storage: Store at or below -20 ºC. Solubility: Soluble Section 68B of the Patents Act of 1953 in New Zealand together in DMSO at 25 mg/mL; very poorly soluble in ethanol; with the amendment of same by the Statutes Amendment Bill of soluble in water at 200 mg/mL; buffers, serum, or other 2002; (vii) such related legislation and/or case law as may be or additives may increase or decrease the aqueous solubility. become applicable in the aforementioned countries; and (viii) such Disposal: A similar laws and rules as may apply in various other countries. • Dovitinib is a small-molecule multitargeted receptor tyrosine • Not available in some countries; not available to some institutions; kinase inhibitor. not available for some uses. • Dovitinib inhibited proliferation of ZNF198-FGFR1 and BCR- OH H FGFR1 transformed Ba/F3 cells with IC50 values of 150 nM OH N O H C and 90 nM, respectively. The phosphorylation of each fusion 3 gene, ERK, and STAT5 was inhibited as well at the same time. O Dovitinib also inhibited proliferation of the FGFR1OP2-FGFR1- N

positive KG1 and KG1A cell lines and induced apoptosis. F NH N 2 N N CH Furthermore, dovitinib significantly inhibited the growth of H 3 primary cells from 8p11 myeloproliferative syndrome (EMS) patients dose-dependently. Chase, A. et al., “Activity of TKI258 Dox — see Doxorubicin, Hydrochloride Salt against primary cells and cell lines with FGFR1-fusion genes (Cat. No. D-4000 on page 33) and Doxorubicin, Free Base associated with the 8p11 myeloproliferative syndrome.” (Cat. No. D-4099 on page 32). Blood 110: 3729‑3734 (2007). Doxil — see Doxorubicin, Hydrochloride Salt • Dovitinib potently inhibits receptor tyrosine kinases including (Cat. No. D-4000 on page 33) and see its active ingredient, FLT3, c-KIT, CSF-1R/c-fms, FGFR1, FGFR3, VEGFR1/ namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). Flt1,VEGFR2/Flk1, VEGFR3/Flt4, PDGFRβ, and PDGFRα with IC50 values of 1, 2, 36, 8, 9, 10, 13, 8, 27, and 210 nM, D-4099 Doxorubicin, Free Base, >99% respectively. Dovitinib selectively blocked the growth of wild- Synonyms: [Dox] [14-Hydroxydaunomycin] type (WT) or activated mutant FGFR3-transformed B9 cells and human myeloma cell lines. Dovitinib was an effective treatment [14-Hydroxydaunorubicine] in a xenograft mouse model of FGFR3 multiple myeloma (MM). Related Terms: [Adriacin] [Adriamycin] [Adriblastin] Trudel, S. et al., “CHIR-258, a novel, multitargeted tyrosine kinase [Adriblastina] [Caelyx] [Doxil] [Farmiblastina] inhibitor for the potential treatment of t(4;14) multiple myeloma.” [Lipodox] [Myocet] [Rubex] Blood 105: 2941‑2948 (2005). • Dovitinib treatment showed antitumor and antiangiogenic Size US$ ¤ £ ¥ activities in xenograft models of human colon cancer. Dovitinib 25 mg 51 39 34 5,700 inhibited vascular endothelial growth factor receptor 1/2, fibroblast 50 mg 74 57 49 8,300 growth factor receptor 1/3, platelet-derived growth factor receptor 100 mg 108 83 71 12,100 β (PDGFR-β), the phosphorylation of PDGFR-β and extracellular 200 mg 176 136 116 19,700 signal-regulated kinase (ERK) in tumors. Lee, S.H. et al., “In 250 mg 198 153 131 22,100 vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon 500 mg 355 274 235 39,700 cancer models.” Clin. Cancer Res. 11: 3633‑3641 (2005). 1 g 544 421 360 60,800 • Dovitinib was examined on two human leukemic cell lines with 2 g 986 762 652 110,200 differing FLT3 mutational status in vitro and in vivo, including 5 g 1790 1384 1183 200,100 MV4;11 cells expressing FLT3 internal tandem duplications (ITD) NOTE: Euro, Pound and Yen prices are revised regularly. and RS4;11 cells with wild-type (WT) FLT3. Antiproliferative Please visit www.LCLabs.com for our current prices. activity of dovitinib against MV4;11 was about 24-fold greater M.W. 543.52 c27H29NO11 [23214-92-8] than against RS4;11. Lopes de Menezes, D.E. et al., “CHIR- M.I. 14: 3439 258: a potent inhibitor of FLT3 kinase in experimental tumor Storage: Store at or below -20 ºC. Solubility: Soluble in xenograft models of human acute myelogenous leukemia.” DMSO. Disposal: A Clin. Cancer Res. 11: 5281‑5291 (2005). • Dovitinib significantly inhibited KMS-11-luc tumor growth and • This is the free base form of doxorubicin; please see our product improved animal survival at doses that inhibited FGFR3 signaling Doxorubicin, Hydrochloride Salt, Cat. No. D-4000 on page 33, in KMS-11-luc tumors in vivo. Xin, X. et al., “CHIR-258 is for further technical information. The hydrochloride salt form efficacious in a newly developed fibroblast growth factor receptor of doxorubicin, not the free base, is used in the doxorubicin 3-expressing orthotopic multiple myeloma model in mice.” formulation for use in humans. Clin. Cancer Res. 12: 4908‑4915 (2006). • Doxorubicin is the active ingredient in the drug products ® • This dovitinib product is the lactate salt, whose CAS number sold under the trade name Adriamycin and the other trade is given above. We also offer the free base – please see names listed above under “Related Terms”. This drug has been

32 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

approved in at least one country for use in patients with a wide • Combination with estradiol was found to enhance the apoptotic range of cancers. NOTE: THE DOXORUBICIN, FREE BASE action of doxorubicin in estrogen-resistant MCF-7/LS cells but not RESEARCH COMPOUND SOLD BY LC LABORATORIES IS in the estrogen-dependent MCF-7 breast cancer cells. NF-kB may NOT ADRIAMYCIN® NOR ANY OTHER DRUG PRODUCT be a potential target for estradiol and doxorubicin in the therapy SPECIFIED BY THE TRADE NAMES LISTED ABOVE of the resistant breast cancer. Scherbakov, A.M. et al., “Oestrogen UNDER “RELATED TERMS” AND IS NOT FOR HUMAN treatment enhances the sensitivity of hormone-resistant breast USE. cancer cells to doxorubicin.” Biosci. Rep.: Jul 27 (2010) [Epub • NOTE: the trade names listed above under “Related Terms” are ahead of print]. for doxorubicin-containing drug products and they may apply • When patients were treated for breast or ovarian cancer, variously to one or another form of doxorubicin, such as the free lymphoma, myeloma or sarcoma, the risk of cardiotoxicity was base, hydrochloride salt or other salt form. significantly greater with doxorubicin-containing regimens and • This doxorubicin product is the free base, whose CAS number is bolus administration than non-anthracycline regimens. Smith, L.A. given above. The CAS number of the hydrochloride salt is 25316- et al., “Cardiotoxicity of anthracycline agents for the treatment 40-9. of cancer: systematic review and meta-analysis of randomised controlled trials.” BMC Cancer 10: 337 (2010). • Several CAS numbers previously assigned to doxorubicin free base, namely 23257-17-2, 24385-08-8, 25311-50-6 and • Doxorubicin hydrochloride is the active ingredient in the drug 29042‑30‑6, have been deleted by CAS and are no longer in use. sold under the tradenames Adriamycin® and Rubex®. This drug has been approved in at least one country for use in patients • Sold for laboratory or manufacturing purposes only; not for with a wide range of cancers. NOTE: THE DOXORUBICIN, human, medical, veterinary, food, or household use. HYDROCHLORIDE SALT RESEARCH COMPOUND SOLD CH ® 3 BY LC LABORATORIES IS NOT ADRIAMYCIN NOR ® OH RUBEX AND IS NOT FOR HUMAN USE. O H • Our doxorubicin product is the hydrochloride salt, whose CAS OCH O OH O NH number is given above. The CAS number of the free base is 3 2 23214-92-8. • Other CAS numbers previously assigned to doxorubicin, namely 23257-17-2, 24385-08-8, 25311-50-6, and 29042-30-6, have been OH OH deleted by CAS and are no longer in use. O OH O • We note that one of our competitors, Medical Isotopes, as of D-4000 Doxorubicin, Hydrochloride Salt, >99% October 31, 2011, is claiming 99.7% purity for its Doxorubicin, Hydrochloride Salt. This claim is not credible in general chemical [Adriacin] [Adriamycin] [Adriblastin] [Adriblastina] terms for this complex organic compound, nor in terms of the [Caelyx] [Dox] [Doxil] [Farmiblastina] [FI-106] sensitivity and reproducibility of generally utilized analytical [14-Hydroxydaunomycin] [Lipodox] [Myocet] [Rubex] techniques. • Sold for laboratory or manufacturing purposes only; not for Size US$ ¤ £ ¥ human, medical, veterinary, food, or household use. 25 mg 51 39 34 5,700 CH 50 mg 74 57 49 8,300 3 OH 100 mg 108 83 71 12,100 O H 200 mg 176 136 116 19,700 OCH O OH O NH 250 mg 198 153 131 22,100 3 2

500 mg 355 274 235 39,700 . HCl 1 g 544 421 360 60,800 2 g 986 762 652 110,200 OH OH 5 g 1790 1384 1183 200,100 O OH O NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. dPAc — see Prostratin (Cat. No. P-4462 on page 94).

M.W. 579.98 C27H29NO11•HCl [25316-40-9] DQ-2805 — see Irinotecan, Hydrochloride Salt, Trihydrate M.I. 14: 3439 (Cat. No. I-4122 on page 57). WARNING: Light-sensitive; minimize light exposure during Elactocin — see Leptomycin B (Cat. No. L-6100 on page 63). handling. Elidel — see its active ingredient, namely Pimecrolimus Storage: Store at or below -20 ºC. Solubility: Soluble (Cat. No. P-6040 on page 91). in DMSO at 100 mg/mL; very poorly soluble in ethanol; soluble in water at 10 mg/mL with slight warming; buffers, Ellence — see its active ingredient, namely Epirubicin, serum, or other additives may increase or decrease the Hydrochloride Salt (Cat. No. E-8000 on page 35). aqueous solubility. Disposal: A Eloxatin — see its active ingredient, namely Oxaliplatin • Doxorubicin is an anthracycline antibiotic. It is used in the (Cat. No. O-7111 on page 79). treatment of a wide range of cancers. Di Marco, A. et al., “Adriamycin (NSC-123,127): a new antibiotic with antitumor Eloxatine — see Oxaliplatin (Cat. No. O-7111 on page 79). activity.” Cancer Chemother. Rep. 53: 33-37 (1969). Elplat — see Oxaliplatin (Cat. No. O-7111 on page 79). • Doxorubicin inhibited DNA and RNA but not protein synthesis in intact cells. Momparler, R.L. et al., “Effect of adriamycin on DNA, Endeavor — see its active ingredient, namely Zotarolimus, Free Base (Cat. No. Z-9040 on page 128). RNA, and protein synthesis in cell-free systems and intact cells.” Cancer Res. 36: 2891-2895 (1976). • Doxorubicin-conjugated HIV(P4/D10) antibody neutralized HIV- 1IIIB and inhibited HIV replication in vitro. It also protected mice from challenge with HIV-1IIIB/MuLV in vivo. Johansson, S. et al., “Elimination of HIV-1 infection by treatment with a doxorubicin- conjugated anti-envelope antibody.” AIDS 20: 1911-1915 (2006).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 33 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

RAMBA VN/66-1 in hormone-insensitive PC-3 prostate cancer E-3866 Entinostat, Free Base, >99% cells and tumours.” Br. J. Cancer 98: 1234-1243 (2008). [Histone Deacetylase Inhibitor I] [MS 275-27] • Another CAS number previously assigned to entinostat, 442532- [MS-275] [MS-27-275] [SNDX 275] 99-2, has been deleted by CAS and is no longer in use. Size US$ ¤ £ ¥ • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. 25 mg 69 51 44 5,400 • This product is offered for R&D use in accordance with (i) 35 50 mg 107 80 69 8,400 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 100 mg 159 119 102 12,400 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 200 mg 246 184 158 19,200 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 1 g 655 489 420 51,100 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 2 g 1050 784 673 81,900 and other common law exemptions of Canadian patent law; (vi) 5 g 2240 1672 1436 174,800 Section 68B of the Patents Act of 1953 in New Zealand together NOTE: Euro, Pound and Yen prices are revised regularly. with the amendment of same by the Statutes Amendment Bill of Please visit www.LCLabs.com for our current prices. 2002; (vii) such related legislation and/or case law as may be or M.W. 376.41 C H N O [209783-80-2] become applicable in the aforementioned countries; and (viii) such 21 20 4 3 similar laws and rules as may apply in various other countries. Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 25 mg/mL with slight warming; very poorly • Not available in some countries; not available to some institutions; soluble in ethanol; very poorly soluble in water; maximum not available for some uses. solubility in plain water is estimated to be about 10‑20 µM; buffers, serum, or other additives may increase or O

decrease the aqueous solubility. Disposal: A N H

NH H N O N • Entinostat is a synthetic benzamide derivative that inhibited 2 partially purified human histone deacetylase (HDA) with an IC50 of 2 µM and induced hyperacetylation of nuclear histones in tumor O cell lines. Entinostat inhibited the proliferation of various human E-4506 Enzastaurin, Free Base, >99% tumor cell lines such as A2780, Calu-3, HL-60, and K562 (IC50 values were 0.0415 µM, 0.195 µM, 0.212 µM, and 0.589 µM, [D04014] [LY-317615] respectively). Entinostat also inhibited the growth of human tumor xenografts in nude mouse. Saito A. et al., “A synthetic inhibitor of Size US$ ¤ £ ¥ histone deacetylase, MS-27-275, with marked in vivo antitumor 10 mg 64 49 42 7,200 activity against human tumors.” Proc. Natl. Acad. Sci. USA 25 mg 118 91 78 13,200 96: 4592-4597 (1999). E-3866-2009-10-08-kedREV.SKC 50 mg 212 164 140 23,700 • Entinostat inhibits tumor growth by inducing tumor suppressors 100 mg 388 300 257 43,400 p21WAF1/CIP1 and gelsolin through acetylation of histones and 200 mg 682 527 451 76,200 changing the cell cycle distribution, decrease of S-phase cells and increase of G1-phase cells. Saito A. et al., “A synthetic inhibitor 300 mg 890 688 588 99,500 NOTE: Euro, Pound and Yen prices are revised regularly. of histone deacetylase, MS-27-275, with marked in vivo antitumor Please visit www.LCLabs.com for our current prices. activity against human tumors.” Proc. Natl. Acad. Sci. USA 96: 4592-4597 (1999). M.W. 515.60 c32H29N5O2 [170364-57-5] • Entinostat inhibited the proliferation of human breast cancer Storage: Store at or below -20 °C. Solubility: Soluble in cells by inducing the expression of transforming growth factor DMSO at 7.1 mg/mL with warming; very poorly soluble in (TGF)-β type II receptor (TβRII) mRNA, but not TGF-β type I ethanol; very poorly soluble in water; maximum solubility receptor mRNA. Lee B.I. et al., “MS-275, a histone deacetylase in plain water is estimated to be about 1-10 µM; buffers, inhibitor, selectively induces transforming growth factor beta type serum, or other additives may increase or decrease the II receptor expression in human breast cancer cells.” Cancer Res. aqueous solubility. Disposal: A 61: 931-934 (2001). • Enzastaurin inhibits PKCβ, PKCα, PKCγ and PKCε with IC50s • Entinostat inhibited the proliferation of four glioma cell lines of 0.006, 0.039, 0.083 and 0.110 µM, respectively. Enzastaurin (U87MG, C6, F98, and SMA-560) with an IC90 of 3.75 µM. Its apparently inhibits tumor growth via multiple mechanisms: antiproliferative effect was mediated by G0-G1 cell cycle arrest suppression of tumor cell proliferation, induction of tumor and apoptosis. Eyüpoglu I.Y. et al., “Experimental therapy of cell apoptosis and inhibition of tumor-induced angiogenesis. malignant gliomas using the inhibitor of histone deacetylase MS- Graff, J.R. et al., “The protein kinase Cbeta-selective inhibitor, 275.” Mol. Cancer Ther. 5: 1248-1255 (2006). enzastaurin (LY317615.HCl), suppresses signaling through the • The toxicities of entinostat in patients included infections AKT pathway, induces apoptosis, and suppresses growth of and neurologic toxicity, fatigue, anorexia, nausea, vomiting, human colon cancer and glioblastoma xenografts.” Cancer Res. hypoalbuminemia, and hypocalcemia. Gojo I. et al., “Phase 1 and 65: 7462‑7469 (2005). pharmacologic study of MS-275, a histone deacetylase inhibitor, • Enzastaurin induces apoptosis in multiple myeloma (MM) in adults with refractory and relapsed acute leukemias.” Blood cell lines by inhibiting signaling through the AKT pathway, 109: 2781-2790 (2007). which is caspase-independent. Rizvi M.A. et al., “Enzastaurin • Entinostat demonstrated dramatic anti-rheumatic activities in (LY317615), a protein kinase Cbeta inhibitor, inhibits the AKT both mouse and rat collagen induced arthritis (CIA) models. pathway and induces apoptosis in multiple myeloma cell lines.” Lin H.S. et al., “Anti-rheumatic activities of histone deacetylase Mol. Cancer Ther. 5: 1783‑1789 (2006). (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents.” • Enzastaurin has an antitumor effect on Waldenström Br. J. Pharmacol. 150: 862-872 (2007). macroglobulinemia both in vitro and in vivo. Moreau, A.S. et al., • The combination treatment of PC-3 prostate cancer cells or “Protein kinase C inhibitor enzastaurin induces in vitro and in vivo tumors with retinoic acid metabolism-blocking agent (RAMBA) antitumor activity in Waldenström macroglobulinemia.” Blood VN/66-1 and entinostat resulted in a significant inhibition in 109: 4964‑4972 (2007). cell proliferation and tumor volume compared with control and • Enzastaurin enhances the antiangiogenic effects of radiation by was more effective than either drug alone. Khandelwal A. et al., radiosensitizing human endothelial cells in pancreatic cancer “MS-275 synergistically enhances the growth inhibitory effects of xenografts. Spalding, A.C. et al., “Enzastaurin, an inhibitor of PKCbeta, enhances antiangiogenic effects and cytotoxicity of

34 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

radiation against endothelial cells.” Transl. Oncol. 1: 195‑201 (2008). E-8000 Epirubicin, Hydrochloride Salt, >99% • Enzastaurin had a synergistic inhibitory effect with the EGFR Synonyms: [4'-Epidoxorubicin] inhibitor gefitinib on the proliferation of parental and gefitinib- Related Terms: [Ellence] [Epiadriamycin] resistant (GR) cancer cells. Enzastaurin also demonstrated [Epirubicin Ebewe] [Pharmorubicin] [Ridorubicin] antitumour activity cooperatively with gefitinib in mice grafted with GEO and GEO-GR colon tumours. Gelardi T. et al., Size US$ ¤ £ ¥ “Enzastaurin inhibits tumours sensitive and resistant to anti-EGFR 5 mg 53 40 34 5,100 drugs.” Br. J. Cancer 99: 473-480 (2008). 10 mg 86 64 55 8,300 • Fifty-five patients with relapsed or refractory diffuse large B-cell 25 mg 178 133 115 17,100 lymphoma (DLBCL) were treated with enzastaurin. Of these, 12 50 mg 275 206 177 26,500 patients showed prolonged freedom from progression (FFP) (FFP 100 mg 358 268 231 34,500 => 2 cycles, one cycle = 28 days). Enzastaurin was well-tolerated. Robertson M.J. et al., “Phase II study of enzastaurin, a protein 200 mg 562 421 362 54,100 kinase C beta inhibitor, in patients with relapsed or refractory 500 mg 1180 885 761 113,600 diffuse large B-cell lymphoma.” J. Clin. Oncol. 25: 1741‑1746 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. (2007). • Sixty patients with relapsed or refractory mantle cell lymphoma M.W. 579.98 C27H29NO11•HCl [56390-09-1] (MCL) were treated with enzastaurin. Enzastaurin had a M.I. 14: 3623 favorable toxicity profile with minimal hematological toxicity. Storage: Store at or below -20 ºC. Solubility: Soluble in Twenty-two patients were FFP for => 3 cycles, 6 of 22 were DMSO. Disposal: A FFP for >6 months. Two patients remained on treatment and FFP at >23 months. Morschhauser F. et al., “A phase II study • Epirubicin is an anthracycline drug used for cancer chemotherapy. of enzastaurin, a protein kinase C beta inhibitor, in patients • Epirubicin-containing regimens are better than those containing with relapsed or refractory mantle cell lymphoma.” Ann. Oncol. cyclophosphamide, methotrexate and fluorouracil (CMF) 19: 247‑253 (2008). for treatment of early breast cancer. “Polychemotherapy • Our enzastaurin product is the free base, whose CAS number for early breast cancer: an overview of the randomised is given above. The CAS number of the dihydrochloride salt is trials. Early Breast Cancer Trialists’ Collaborative Group.” 365253-37-8. Lancet 352: 930‑942 (1998). • Sold for laboratory or manufacturing purposes only; not for • The mechanisms of antitumor activity of anthracyclines may human, medical, veterinary, food, or household use. include 1) inhibition synthesis of macromolecules by intercalation into DNA; 2) DNA damage or lipid peroxidation by generation • This product is offered for R&D use in accordance with (i) 35 of free radicals; 3) DNA cross-linking; 4) DNA binding and USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese alkylation; 5) interference with DNA unwinding, DNA strand Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent separation, and helicase activity; 6) membrane effects; and 7) Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. initiation of DNA damage by inhibition of topoisomerase II, and Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) thus induction of apoptosis. Minotti, G. et al., “Anthracyclines: and other common law exemptions of Canadian patent law; (vi) molecular advances and pharmacologic developments in antitumor Section 68B of the Patents Act of 1953 in New Zealand together activity and cardiotoxicity.” Pharmacol. Rev. 56: 185‑229 (2004). with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or • Several clinical trials have demonstrated that epirubicin-containing become applicable in the aforementioned countries; and (viii) such regimens at equimolar doses achieved equivalent objective similar laws and rules as may apply in various other countries. response rates and overall median survival as doxorubicin- containing regimens in the treatment of advanced and early breast • Not available in some countries; not available to some institutions; cancer, non-small cell lung cancer and small cell lung cancer, not available for some uses. non-Hodgkin’s lymphoma, gastric cancer, ovarian cancer and H nonresectable primary hepatocellular carcinoma. Plosker, G.L.

N and Faulds, D., “Epirubicin. A review of its pharmacodynamic O O and pharmacokinetic properties, and therapeutic use in cancer chemotherapy.” Drugs 45: 788‑856 (1993). • Epirubicin and doxorubicin are two major anthracyclines. At

N N equimolar doses, these two anthracyclines showed similar response rates. The major side effects of anthracyclines are cardiotoxicity Me and myelosuppression. Epirubicin, having less toxicity at similar doses, represents an alternative to doxorubicin for breast cancer N treatment. Kaklamani, V.G. and Gradishar, W.J. “Epirubicin versus N doxorubicin: which is the anthracycline of choice for the treatment of breast cancer?” Clin. Breast Cancer 4: S26‑S33 (2003). E-4506-2009-10-08-kedREV.SKC• Epirubicin is the active ingredient in the drug product sold under the trade name Ellence® and the other trade names listed above Epiadriamycin — see its active ingredient, namely Epirubicin, under “Related Terms”. This drug is currently approved in at least Hydrochloride Salt (Cat. No. E-8000 on page 36). one country for use in patients with breast cancer, and is used for 4'-Epidoxorubicin — see Epirubicin, Hydrochloride Salt treatment of various other cancers. NOTE: THE EPIRUBICIN, (Cat. No. E-8000 on page 36). HYDROCHLORIDE SALT RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ELLENCE® NOR ANY Epirubicin Ebewe — see its active ingredient, namely Epirubicin, OTHER DRUG PRODUCT SPECIFIED BY THE TRADE Hydrochloride Salt (Cat. No. E-8000 on page 36). NAMES LISTED ABOVE UNDER “RELATED TERMS” AND IS NOT FOR HUMAN USE. • NOTE: the trade names listed above under “Related Terms” are for epirubicin-containing drug products and they may apply variously to one or another form of epirubicin, such as the free base, hydrochloride salt or other salt form.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 35 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• This epirubicin product is the hydrochloride salt, whose CAS to taxol (EC50 = 20 nM for Hela cells and 15 nM for Hs578T). number is given above. The CAS number of the free base is However, epothilone B retains a much greater mitotic arrest at the 56420-45-2. G2-M transition and toxicity against P-glycoprotein-expressing • Sold for laboratory or manufacturing purposes only; not for multiple drug resistant KBV-1 cells (EC50 = 92 nM and 58 human, veterinary, food, or household use. nM, respectively) than paclitaxel (EC50 = 17 uM and 23 uM, respectively). Bollag, D.M. et al., “Epothilones, a new class of • This product is offered for R&D use in accordance with (i) 35 microtubule-stabilizing agents with a taxol-like mechanism of USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese action.” Cancer Res. 55: 2325-2333 (1995). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Two acquired b-tubulin mutations [b274(Thr-->Ile) and b282(Arg-- Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) >Gln)] near the taxane binding site exhibit impaired epothilone- and and other common law exemptions of Canadian patent law; (vi) taxane-driven tubulin polymerization. Giannakakou, P. et al., “A Section 68B of the Patents Act of 1953 in New Zealand together common pharmacophore for epothilone and taxanes: molecular with the amendment of same by the Statutes Amendment Bill of basis for drug resistance conferred by tubulin mutations in human 2002; (vii) such related legislation and/or case law as may be or cancer cells.” Proc. Natl. Acad. Sci. USA 97: 2904-2909 (2000). become applicable in the aforementioned countries; and (viii) such • Purified tubulin from parental 1A9 human ovarian carcinoma cells similar laws and rules as may apply in various other countries. demonstrated paclitaxel-driven increased polymerization while the • Not available in some countries; not available to some institutions; resistant cell tubulin with a mutation at 270 (Phe --> Val) or 364 not available for some uses. (Ala --> Thr) barely polymerized under identical conditions. In contrast, the resistant cells retained sensitivity to epothilone B and CH 3 the assembly was increased. Giannakakou, P. et al., “Paclitaxel- OH O resistant human ovarian cancer cells have mutant beta-tubulins that H exhibit impaired paclitaxel-driven polymerization.” OCH O OH O NH J. Biol. Chem. 272: 17118-17125 (1997). 3 2 • Epothilone B inhibited the growth of paclitaxel-sensitive human . HCl carcinoma cell lines including A549 (lung), NCI-H460 (Lung),

OH HCT-116 (colon), DU145 (prostate), PC-3M (prostate), MDA- OH MB-231 (breast), BT-20 (breast), ZR-75-1 (breast), T-24 (bladder), O OH O and A-431 (epidermoid) with IC50’s ranging from 0.13 nM to 0.64 EPO-906 — see Epothilone B, Free Base nM. It also inhibited the growth of paclitaxel-resistant human (Cat. No. E-5500 on page 36). cancer cell lines including CCRF-CEM (leukemia), CCRF-CEM/ VBL100, SW620 (colon), SW620AD-300, KB-31, KB-8511, 1A9 EpoB — see Epothilone B, Free Base (Cat. No. E-5500 on page 36). (ovarian), 1A9PTX22, MCF-7 (breast), MCF-7/ADR, and HCT-15 (colon) with IC ’s of 0.06 nM to 2.9 nM. Altmann, K.H. et al., Eposin — see its active ingredient, namely Etoposide 50 (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, “Epothilones and related structures--a new class of microtubule Free Acid (Cat. No. E-4444 on page 39). inhibitors with potent in vivo antitumor activity.” Biochim. Biophys. Acta 1470: M79-M91 (2000). E-5500 Epothilone B, Free Base, >99% • Diarrhea is the dose-limiting toxicity for epothilone B in clinical [EPO-906] [EpoB] [Patupilone] trials for patients with lung, ovarian and prostate cancers. Larkin, J.M.G. et al., “Patupilone” Drugs Fut. 32: 323 (2007). Size US$ ¤ £ ¥ • Another CAS number previously assigned to epothilone B, 1 mg 32 25 21 3,600 681125-91-7, has been deleted by CAS and is no longer in use. 2 mg 51 39 34 5,700 • Sold for laboratory or manufacturing purposes only; not for 5 mg 73 56 48 8,200 human, medical, veterinary, food, or household use. 10 mg 117 90 77 13,100 • This product is offered for R&D use in accordance with (i) 35 25 mg 244 189 161 27,300 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 50 mg 416 322 275 46,500 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 100 mg 678 524 448 75,800 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 200 mg 1130 873 747 126,300 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) 300 mg 1611 1245 1065 180,100 Section 68B of the Patents Act of 1953 in New Zealand together 500 mg 2550 1971 1686 285,100 with the amendment of same by the Statutes Amendment Bill of NOTE: Euro, Pound and Yen prices are revised regularly. 2002; (vii) such related legislation and/or case law as may be or Please visit www.LCLabs.com for our current prices. become applicable in the aforementioned countries; and (viii) such M.W. 507.68 C27H41NO6S [152044-54-7] similar laws and rules as may apply in various other countries. M.I. 14: 3628 • Not available in some countries; not available to some institutions; Storage: Store at or below -20 ºC. Solubility: Soluble not available for some uses.

in DMSO at 40 mg/mL; soluble in ethanol at 40 mg/mL; CH very poorly soluble in water; maximum solubility in plain O 3 S CH water is estimated to be about 10-50 µM; buffers, serum, 3 H C or other additives may increase or decrease the aqueous 3 H C OH N 3 CH solubility. Disposal: A H C 3 O 3 • Epothilones A-F are anticancer drugs. They induce microtubule CH 3 polymerization at submicromolar concentrations and lead to death O OH O of cancer cells. Goodin, S. et al., “Epothilones: mechanism of action and biologic activity.” J. Clin. Oncol. 22: 2015-2025 (2004). • Epothilone B possess essentially all the biological effects of taxol both in vitro and in cultured cells. Epothilone B caused cell cycle arrest at the G2-M transition (EC50 = 32 nM for Hela cells and 3 nM for Hs578T), similar to taxol (EC50 = 7 nM for Hela cells and 10 nM for Hs578T). Epothilone B leads to cytotoxicity (EC50 = 40 nM for Hela cells and 6 nM for Hs578T), also similar

36 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

E-5880 (R,S)-Equol, >99% E-4997 Erlotinib, Free Base, >99% Synonyms: [CP-358774] [OSI-774] [Ro 50-8231] Size US$ ¤ £ ¥ 100 mg 64 46 38 8,000 Related Terms: [Tarceva] 300 mg 172 125 102 21,400 Size US$ ¤ £ ¥ 500 mg 225 163 134 28,000 500 mg 37 28 24 3,700 1 g 362 262 216 45,000 1 g 55 41 35 5,400 5 g 625 453 372 77,700 2 g 96 72 62 9,500 10 g 980 710 584 121,800 5 g 189 141 121 18,700 25 g 1975 1430 1176 245,500 10 g 350 262 225 34,500 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 25 g 825 616 530 81,400 M.W. 242.27 C H O [94105-90-5] 100 g 2620 1958 1682 258,600 15 14 3 NOTE: Euro, Pound and Yen prices are revised regularly. M.I. 14: 3644 Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 °C. Solubility: Soluble in M.W. 393.44 c22H23N3O4 [183321-74-6] DMSO at 200 mg/mL; soluble in ethanol at 200 mg/mL; M.I. 14: 3672 very poorly soluble in water; maximum solubility in plain water is estimated to be about 20-50 µM; buffers, serum, Storage: Store at or below -20 ºC. Solubility: Soluble in or other additives may increase or decrease the aqueous DMSO at 100 mg/mL; soluble in ethanol at 10 mg/mL with solubility. Disposal: A warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-20 µM; buffers, • Urinary metabolite of daidzein, produced by humans and serum, or other additives may increase or decrease the horses. Heinonen, S. et al., “Identification of isoflavone aqueous solubility. Disposal: A metabolites dihydrodaidzein, dihydrogenistein, 6'-OH-dma, and cis-4-OH-equol in human urine by gas chromatography- • This is the free base form of erlotinib; please see our product, mass spectrometry using authentic reference compounds.” Erlotinib, Hydrochloride Salt (Cat. No. E-4007 on page 38). for Anal. Biochem. 274: 211‑219 (1999). further technical information. The hydrochloride salt form of erlotinib, not the free base, is used in the erlotinib formulation for • This product is a racemic mixture of the R- and S-enantiomers. use in humans. However, the naturally-occurring form or equol from horse urine consists of a single stereoisomer, namely the S-isomer. While • Erlotinib (as the hydrochloride salt) is the active ingredient in ® the chemical properties of the S-isomer are essentially identical the drug product sold under the trade name Tarceva . This drug to those of the racemic mixture (except for rotation of plane has been approved in at least one country for use in patients polarized light, melting point, etc.), the biological properties of with pancreatic cancer, non-small cell lung cancer and several the naturally-occurring S-isomer are quite likely to be somewhat other types of cancer. NOTE: THE ERLOTINIB, FREE BASE different from those of the racemic mixture. RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT TARCEVA® AND IS NOT FOR HUMAN USE. • The CAS number of our racemic Equol product is 94105-90-5, as noted near the top of this page. The CAS number of the naturally- • This erlotinib product is the free base, whose CAS number is given occurring S-isomer is 531-95-3. above. The CAS number of the hydrochloride salt is 183319-69-9. • Another CAS number previously assigned to (R,S) Equol, namely • Related CAS numbers: 248594-19-6 for the erlotinib mesylate. 66036-38-2, has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese OH Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) HO O Section 68B of the Patents Act of 1953 in New Zealand together Eril — see its active ingredient, namely Fasudil, with the amendment of same by the Statutes Amendment Bill of Monohydrochloride Salt (Cat. No. F-4660 on page 40) 2002; (vii) such related legislation and/or case law as may be or and HA-1077 (Cat. No. H-2330 on page 52). become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. Erivedge — see its active ingredient, namely Vismodegib, Free Base (Cat. No. V-4050 on page 121). • Not available in some countries; not available to some institutions; not available for some uses.

H C O N 3 O

O N H C O 3 N H

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 37 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; E-4007 Erlotinib, Hydrochloride Salt, >99% not available for some uses. [CP-358774] [OSI-774] [Tarceva] O N O Size US$ ¤ £ ¥ O N 500 mg 37 28 24 3,700 O 1 g 41 35 5,400 NH 55 .HCl 2 g 96 72 62 9,500 5 g 189 141 121 18,700 10 g 350 262 225 34,500 Etophos — see its active ingredient, namely Etoposide 25 g 825 616 530 81,400 (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, 100 g 2620 1958 1682 258,600 Free Acid (Cat. No. E-4444 on page 39). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Etopofos — see its active ingredient, namely Etoposide (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, M.W. 429.90 c22H23N3O4 •HCl [183319-69-9] Free Acid (Cat. No. E-4444 on page 39). Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 18 mg/mL after warming; very poorly soluble Etopophos — see its active ingredient, namely Etoposide (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, in ethanol; very poorly soluble in water; maximum water Free Acid (Cat. No. E-4444 on page 39). solubility is estimated to be about 5‑20 µM; buffers, serum or other additives may increase or decrease the aqueous E-4488 Etoposide, >99% solubility. Disposal: A Synonyms: [BMY-40481] [Etoposide • Erlotinib specifically targets the epidermal growth factor 4'-Dihydrogenphosphate] [VP-16] [VP-16-213] receptor tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds Related Terms: [Eposin] [Etophos] [Etopofos] reversibly to the adenosine triphosphate binding site of [Etopophos] [Lastet] [Novaplus] [Toposar] [Vepesid] the receptor. Raymond, E. et al., “Epidermal growth factor [Zuyeyidal] receptor tyrosine kinase as a target for anticancer therapy.” Drugs 60: Suppl. 1 15‑23, discussion 41‑42 (2000). Size US$ ¤ £ ¥ • Erlotinib is a directly acting inhibitor of human EGFR 100 mg 44 34 29 4,900 tyrosine kinase with an IC50 of 2 nM and reduces EGFR 250 mg 87 67 58 9,700 autophosphorylatlon in intact tumor cells with an IC50 of 20 nM. 500 mg 136 105 90 15,200 Moyer, J.D. et al., “Induction of Apoptosis and Cell Cycle Arrest 1 g 228 176 151 25,500 by erlotinib, an Inhibitor of Epidermal Growth Factor Receptor 2 g 414 320 274 46,300 Tyrosine Kinase.” Cancer Res. 57: 4838-4848 (1997). 5 g 890 688 588 99,500 • Erlotinib has recently been shown to be a potent inhibitor of NOTE: Euro, Pound and Yen prices are revised regularly. JAK2-V617F activity. JAK2-V617F is a mutant of tyrosine Please visit www.LCLabs.com for our current prices. kinase JAK2 and is found in most patients with polycythemia M.W. 588.56 c H O [33419-42-0] vera (PV) and a substantial proportion of patients with idiopathic 29 32 13 myelofibrosis or essential thrombocythemia. The study suggests M.I. 14: 3886 that erlotinib may be used for treatment of JAK2-V617F-positive Storage: Store at or below -20 ºC. Solubility: Soluble PV and other myeloproliferative disorders. Li, Z. et al., “Erlotinib in DMSO at 100 mg/mL; very poorly soluble in ethanol; effectively inhibits JAK2V617F activity and polycythemia vera very poorly soluble in water; maximum solubility in plain cell growth.” J. Biol. Chem. 282: 3428–3432 (2007). water is estimated to be 20-50 µM; buffers, serum or other • Found to be a potent inhibitor of EGFR kinase (K = 0.7 nM), additives may increase or decrease the aqueous solubility. i Disposal: A but much weaker for ErbB-2 kinase (Ki = 1 µM) and ErbB-4 kinase (Ki = 1.5 µM). Wood, E.R. et al., “A Unique Structure • This product is etoposide itself; please see Etoposide 4'-Phosphate, for Epidermal Growth Factor Receptor Bound to GW572016 Free Acid (Cat. No. E-4444 on page 39), for further technical (Lapatinib), Relationships among Protein Conformation, Inhibitor information. Both etoposide and etoposide 4'-phosphate are used Off-Rate, and Receptor Activity in Tumor Cells.” in formulations for use in humans. Cancer Res. 64: 6652-6659 (2004). • Etoposide or Etoposide 4'-Phosphate, Free Acid are the active • Erlotinib is the active ingredient in the drug sold under the trade ingredients in the drug products sold under the trade name name Tarceva®. The drug is currently approved in at least one Toposar® and the other trade names listed above under “Related country for use in patients with non-small cell lung cancer, Terms”. These drugs are currently used in patients with a pancreatic cancer and several other types of cancer. NOTE: variety of types of cancer, such as non-lymphocytic leukemia, THE ERLOTINIB, HYDROCHLORIDE SALT RESEARCH Ewing’s sarcoma, testicular cancer, lung cancer, and glioblastoma COMPOUND SOLD BY LC LABORATORIES IS NOT multiforme. NOTE: THE ETOPOSIDE AND ETOPOSIDE TARCEVA® AND IS NOT FOR HUMAN USE. 4'-PHOSPHATE, FREE ACID RESEARCH COMPOUNDS ® • Sold for laboratory or manufacturing purposes only; not for SOLD BY LC LABORATORIES ARE NOT TOPOSAR NOR human, medical, veterinary, food, or household use. ANY OTHER DRUG PRODUCT SPECIFIED BY THE TRADE NAMES LISTED ABOVE UNDER “RELATED TERMS” AND • This product is offered for R&D use in accordance with (i) 35 ARE NOT FOR HUMAN USE. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • NOTE: the trade names listed above under “Related Terms” are Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. for etoposide- or etoposide 4'-phosphate-containing drug products Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and they may apply variously to formulations of etoposide or and other common law exemptions of Canadian patent law; (vi) etoposide 4'-phosphate. Section 68B of the Patents Act of 1953 in New Zealand together • Free etoposide has the CAS number given above. The CAS with the amendment of same by the Statutes Amendment Bill of number of etoposide 4'-phosphate is 117091-64-2. 2002; (vii) such related legislation and/or case law as may be or • Other CAS numbers previously assigned to Etoposide, 35317- become applicable in the aforementioned countries; and (viii) such 32-9, 51854-34-3, 76576-58-4, 121471-01-0, 136598-18-0, and similar laws and rules as may apply in various other countries. 201594-04-9, have been deleted by CAS and are no longer in use.

38 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Sold for laboratory or manufacturing purposes only; not for etoposide 4'-phosphate or etoposide alone. Senter, P.D. et human, medical, veterinary, food, or household use. al., “Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate.” OH Proc. Natl. Acad. Sci. USA 85: 4842‑4846 (1988). H C O OCH 3 3 • Disruption of the murine multidrug resistance protein gene resulted in a two-fold increase in sensitivity to etoposide O H 4'-phosphate. Lorico, A. et al., “Disruption of the murine MRP O (multidrug resistance protein) gene leads to increased sensitivity O to etoposide (VP-16) and increased levels of glutathione.” O Cancer Res. 57: 5238‑5242 (1997). H H O O • A phase III clinical trial showed that patients with advanced O H small-cell lung cancer (SCLC) gained a survival benefit and improved quality of life after treatment with the combination of H C O OH 3 H etoposide, carboplatin and paclitaxel. Reck, M. et al., “Efficient OH palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and Etoposide 4'-Dihydrogenphosphate — see Etoposide (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, 6-years'-follow-up results from a randomised phase III trial.” Free Acid (Cat. No. E-4444 on page 39). Lung Cancer 53: 67‑75 (2006). • NOTE: Etoposide 4'-Phosphate, Free Acid is not a phosphate E-4444 Etoposide 4'-Phosphate, Free Acid, >99% salt of etoposide. The phosphate group is covalently bound to the Synonyms: [BMY-40481] [Etoposide etoposide moiety, and thus etoposide phosphate is chemically 4'-Dihydrogenphosphate] [VP-16] [VP-16-213] different from etoposide, not merely a different salt form. Etoposide itself is not basic and cannot form an acid addition salt Related Terms: [Eposin] [Etophos] [Etopofos] with phosphoric acid or other acids. [Etopophos] [Lastet] [Novaplus] [Toposar] [Vepesid] • Etoposide 4'-phosphate is sometimes referred to, erroneously, as [Zuyeyidal] “etoposide 4'-phosphonate.” The latter nomenclature is chemically not correct. Size US$ ¤ £ ¥ • Etoposide or its 4'-phosphate derivative are the active ingredients 25 mg 84 68 54 6,700 in the drug products sold under the trade name Etopofos® and 100 mg 187 143 118 15,300 the other trade names listed above under “Related Terms”. 300 mg 245 187 154 20,000 These drugs are currently used in patients with a variety of 500 mg 315 240 198 25,700 types of cancer, such as non-lymphocytic leukemia, Ewing’s 1 g 472 360 297 38,600 sarcoma, testicular cancer, lung cancer, and glioblastoma 2 g 864 660 544 70,600 multiforme. NOTE: THE ETOPOSIDE AND ETOPOSIDE 5 g 1780 1359 1121 145,400 4'-PHOSPHATE, FREE ACID RESEARCH COMPOUNDS ® NOTE: Euro, Pound and Yen prices are revised regularly. SOLD BY LC LABORATORIES ARE NOT ETOPOFOS NOR Please visit www.LCLabs.com for our current prices. ANY OTHER DRUG PRODUCT SPECIFIED BY THE TRADE M.W. 668.54 c H O P [117091-64-2] NAMES LISTED ABOVE UNDER “RELATED TERMS” AND 29 33 16 ARE NOT FOR HUMAN USE. M.I. 14: 3886 • NOTE: the trade names listed above under “Related Terms” are Storage: Store at or below -20 ºC. Solubility: Soluble in for etoposide- or etoposide 4'-phosphate-containing drug products water and DMSO. Disposal: A and they may apply variously to formulations of etoposide or • Etoposide 4'-phosphate is a water-soluble prodrug of etoposide etoposide 4'-phosphate. that is rapidly and completely converted to etoposide, the active • Our Etoposide 4'-Phosphate, Free Acid research compound is the parent compound, after intravenous dosing. Unphosphorylated free acid, whose CAS number is given above. The CAS number of etoposide is active in the treatment of many cancers but its use etoposide itself is 33419-42-0. is limited by its lack of water solubility. Etoposide is formulated • Related CAS numbers: the CAS number for the disodium salt of with polyethylene glycol, polysorbate 80, and ethanol, but causes etoposide 4'-phosphate is 122405-33-8. Etoposide 4'-phosphate acidosis when given at high doses. Etoposide and etoposide free acid is more stable than its disodium salt, and the latter is not 4'-phosphate have essentailly identical pharmacokinetic profiles, used clinically. toxicity, and clinical activity. Schacter, L., “Etoposide phosphate: • Other CAS numbers previously assigned to Etoposide what, why, where, and how?” Semin. Oncol. 23: 1‑7 (1996). 4'-Phosphate, Free Acid, namely 122332-48-3, 138067-47-7, and • We also offer the unphosphorylated form of etoposide – see 149027-99-6, have been deleted by CAS and are no longer in use. Etoposide (Cat. No. E-4488 on page 38). • Sold for laboratory or manufacturing purposes only; not for • The conversion of etoposide 4'-phosphate to etoposide occurs human, veterinary, food, or household use. in the GI tract after oral administration. de Jong, R.S. et al., OPO H “Conversion of the prodrug etoposide phosphate to etoposide in 3 2 H C O OCH gastric juice and bile.” Br. J. Cancer 76: 1480‑1483 (1997). 3 3 • Free etoposide inhibits topoisomerase II. A ternary complex of

etoposide, DNA and the topoisomerase II enzyme forms and O prevents re-ligation of the DNA strands. This results in errors in H O DNA synthesis and induces apoptosis of the cancer cell. Nitiss, O J.L., “Targeting DNA topoisomerase II in cancer themotherapy.” O Nat. Rev. Cancer 9: 338‑350 (2009). H H O O • In in vitro studies with the H3347 human colon carcinoma O cell line, etoposide 4'-phosphate was less toxic than etoposide H H C O OH by a factor of greater than 100. A stronger antitumor 3 H response was observed in H3347-bearing mice that were OH treated with a monoclonal antibody plus L6 (anticarcinoma)- alkaline phosphatase conjugate followed 18-24 hr later by etoposide 4'-phosphate when compared to treatment with

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 39 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

O E-4040 Everolimus, >99% HO [Afinitor] [Certican] [RAD001] CH O 3 CH [40-O-(2-hydroxyethyl)-rapamycin] [SDZ-RAD] 3 [Zortress] H O O OH Size US$ ¤ £ ¥ N H 5 mg 48 36 30 4,000 O O O CH O O 3 10 mg 83 63 51 6,900 HO 25 mg 146 111 90 12,200 O OCH 3 50 mg 247 188 153 20,600 100 mg 395 300 244 33,000 250 mg 859 653 531 71,700 300 mg 999 759 618 83,400 Evoltra — see its active ingredient, namely Clofarabine, Free Base 500 mg 1595 1212 987 133,200 (Cat. No. C-1999 on page 22). 1 g 2880 2189 1781 240,500 Exal — see its active ingredient, namely Vinblastine, Sulfate Salt NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. (Cat. No. V-7300 on page 121). Exel-2880 — see Foretinib, Free Base (Cat. No. F-4185 on page 43). M.W. 958.22 c53H83NO14 [159351-69-6] M.I. 14: 3907 Faridak — see Panobinostat, Free Base (Cat. No. P-3703 on page 80). Storage: Store at or below -20 °C. Solubility: Soluble in Farmiblastina — see Doxorubicin, Hydrochloride Salt DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; (Cat. No. D-4000 on page 33) and see its active ingredient, very poorly soluble in water; maximum solubility in plain namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). water is estimated to be about 1-10 µM; buffers, serum, or other additives may increase or decrease the aqueous F-4660 Fasudil, Monohydrochloride Salt, >99% solubility. Disposal: A [AT-877] [Eril] • Everolimus is an immunosuppressant analog of rapamycin that [1-(5-Isoquinolinesulfonyl)homopiperazine, blocks growth factor-mediated proliferation of haematopoietic Monohydrochloride Salt] and nonhaematopoietic cells. Chapman T.M. And Perry C.M., “Everolimus.” Drugs 64: 861-872 (2004); discussion 873-874. Size US$ ¤ £ ¥ • Everolimus displays a potent inhibitory effect on posttransplant 250 mg 38 29 25 4,200 lymphoproliferative disorder (PTLD) -derived cells in vitro and in 500 mg 62 48 41 6,900 vivo, in a dose range that can prevent allograft rejection, and may prove effective in both the prevention and treatment of PTLDs 1 g 111 86 73 12,400 in transplant patients. Majewski M. et al., “Immunosuppressive 2 g 194 150 128 21,700 TOR kinase inhibitor everolimus (RAD) suppresses growth 5 g 390 301 258 43,600 of cells derived from posttransplant lymphoproliferative 10 g 660 510 436 73,800 disorder at allograft-protecting doses.” Transplantation NOTE: Euro, Pound and Yen prices are revised regularly. 75: 1710‑1717 (2003). Please visit www.LCLabs.com for our current prices.

• Oral everolimus suppresses in-stent neointimal growth in the rabbit M.W. 327.83 C14H17N3O2S•HCl [105628-07-7] iliac artery. At a dose of 1.5 mg/kg given 1 day before stenting M.I. 14: 3942 followed by 0.75 mg/kg per day for 28 days, everolimus was well Storage: Store at or below -20 °C. Solubility: Very soluble tolerated and was associated with significant neointimal healing. in water, up to 200 mg/mL or more; soluble in DMSO Farb A. et al., “Oral Everolimus Inhibits In-Stent Neointimal up to about 95 mg/mL; not soluble in ethanol; addition Growth.” Circulation 106: 2379-2384 (2002). of an aqueous solution of this monohydrochloride salt • Everolimus is the active ingredient in the drug sold under the into a buffer solution may significantly alter its solubility. trade names Certican®, Afinitor®, Zortress®, and in the drug- Disposal: A ® eluting stent sold under the trade name Xience V . The drug is • Nomenclature. Two names have been widely used for this approved in at least one country for prophylaxis of organ rejection compound, “HA-1077” and “Fasudil”, and these names have in patients who have received a kidney or heart transplant, and the been variously and inconsistently applied to the free base (a form stent has been approved in at least one country for use in patients that LC Labs does not sell), the monohydrochloride salt and the undergoing angioplasty. NOTE: the everolimus sold by LC ® ® ® dihydrochloride salt forms. For many years LC Labs has sold the Laboratories is NOT Certican nor Afinitor nor Zortress and is dihydrochloride salt under the name HA-1077, Dihydrochloride NOT for human use. Salt (Cat. No. H-2330 on page 52). For historical reasons and for • Sold for laboratory or manufacturing purposes only; not for continuity, we have elected to continue using the HA-1077 name human, medical, veterinary, food, or household use. for our dihydrochloride salt product, even though we recently • This product is offered for R&D use in accordance with (i) 35 introduced the monohydrochloride salt form under the name USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Fasudil, Monohydrochloride Salt, as described on this page. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • The monohydrochloride salt is the form used to prepare Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. formulations of this drug for clinical use. Note that the solubility Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) properties of the mono- and di-HCl salts are different. and other common law exemptions of Canadian patent law; (vi) • Kinase inhibitor; has antivasospastic properties. Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of - Asano, T. et al., “Vasodilator actions of HA1077 in vitro 2002; (vii) such related legislation and/or case law as may be or and in vivo putatively mediated by the inhibition of protein become applicable in the aforementioned countries; and (viii) such kinases.” Br. J. Pharmacol. 98: 1091-1100 (1989). similar laws and rules as may apply in various other countries. - Sasaki, Y. and Sasaki, Y., “Inhibition of myosin light chain • Not available in some countries; not available to some institutions; phosphorylation in cultured smooth muscle cells by HA1077, not available for some uses. a new type of vasodilator.” Biochem. Biophys. Res. Commun. 171: 1182‑1187 (1990).

40 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

- Seto, M. et al., “Effects of HA 1077, a protein kinase inhibitor, on myosin phosphorylation and tension in smooth NH muscle.” Eur. J. Pharmacol. 195: 267-272 (1991). N SO - Shibuya, O. et al., “The effects of an intracellular calcium 2 antagonist HA 1077 on delayed cerebral vasospasm in dogs.” Acta Neurochir. 90: 53 (1988). •HCl - Shirotani, M. et al., “A new type of vasodilator, HA 1077, N an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture.” J. Pharmacol. Exp. F-4077 Fenretinide, >99% Ther. 259: 738‑744 (1991). Synonyms: [4-HPR] [McN-R-1967] [MK-4016] - Swärd, K. et al., “Inhibition of Rho-associated kinase [RII retinamide] [Ro 22-4667] blocks agonist-induced Ca2+ sensitization of myosin phosphorylation and force in guinea-pig ileum.” J. Physiol. Size US$ ¤ £ ¥ 522: 33-49 (2000). 10 mg 39 28 23 4,400 - Davies, S.P. et al., “Specificity and mechanism of action of 25 mg 64 46 38 7,300 some commonly used protein kinase inhibitors.” New! Biochem. J. 351: 95-105 (2000). 50 mg 89 64 53 10,100 100 mg 121 87 73 13,700 • Potencies for inhibition of various kinases by Fasudil: 250 mg 233 168 140 26,500 500 mg 335 241 201 38,100

Enzyme IC50 Ki Reference 1 g 545 392 327 61,900 2 g 915 658 550 103,900 Rho-associated 1.9 mM Davies, S.P. et al. Kinase II 5 g 1990 1431 1195 226,100 NOTE: Euro, Pound and Yen prices are revised regularly. Protein Kinase Please visit www.LCLabs.com for our current prices. 4 mM Davies, S.P. et al. C-Related M.W. 391.55 c26H33NO2 [65646-68-6] Mitogen- and Stress- M.I. 15: 4025 Activated Protein 5 mM Davies, S.P. et al. Storage: Store at or below -20 ºC. Solubility: Soluble in Kinase I DMSO at 90 mg/mL; soluble in ethanol at 25 mg/mL with Mitogen Activated warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 1-5 µM; buffers, Protein Kinase- 5 mM Davies, S.P. et al. serum, or other additives may increase or decrease the Activated Protein aqueous solubility. Disposal: A Kinase 1b • Fenretinide is a vitamin A analogue and has been used as a Rho-associated 10.7 mM Swärd, K. et al. chemopreventive retinoid for women at risk of developing Kinase contralateral breast cancer. Fenretinide treatment resulted Myosin Light Chain in a significant risk reduction of second breast cancer in 95.2 mM Swärd, K. et al. Kinase premenopausal women after 15 year followups, which is remarkable at younger ages, and persisted several years after Protein Kinase C 425 mM Swärd, K. et al. treatment cessation. Veronesi, U. et al., "Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast Cyclic AMP- cancer." Ann. Oncol. 17: 1065‑1071 (2006). Dependent Protein 1.6 mM Asano, T. et al. Kinase • Fenretinide is concentrated by breast tissue in patients. Mehta, R.G. et al., "Distribution of fenretinide in Cyclic GMP- the mammary gland of breast cancer patients." Dependent Protein 1.6 mM Asano, T. et al. Eur. J. Cancer 27: 138‑141 (1991). Kinase • The mechanism of action for fenretinide is not yet fully Myosin Light Chain understood. It may inhibit cell growth through induction of 36 mM Asano, T. et al. Kinase apoptosis, not differentiation, and through vitamin A receptor- dependent and -independent mechanisms. Cazzaniga, M. et al., "Fenretinide (4-HPR): a preventive chance for women at genetic • This monohydrochloride salt form is the active ingredient in and familial risk?" J. Biomed. Biotechnol. 2012: 172897 (2012). drug formulations marketed in Japan to treat cerebral vasospasm • Another CAS number previously assigned to Fenretinide, namely following surgery for subarachnoid hemorrhage and associated 1006055-28-2, has been deleted by CAS and is no longer in use. cerebral ischemic symptoms. Zhao, J. et al., “Effect of Fasudil • Sold for laboratory or manufacturing purposes only; not for Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm human, veterinary, food, or household use. and Delayed Cerebral Ischemic Symptoms After Aneurysmal • This product is offered for R&D use in accordance with (i) 35 Subarachnoid Hemorrhage.” Neurologia Medico-Chirurgica USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 46: 421-428 (2006). Also, the monohydrochloride form has been Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent or presently is in human clinical trials for treatment of acute Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. cerebral thrombosis, subarachnoid hemorrhage, and angina Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) pectoris. and other common law exemptions of Canadian patent law; (vi) • Related CAS numbers: 103745-39-7 for the fasudil free base and Section 68B of the Patents Act of 1953 in New Zealand together 203911-27-7 for HA-1077 dihydrochloride salt. with the amendment of same by the Statutes Amendment Bill of • Fasudil is the active ingredient in the drug sold under the trade 2002; (vii) such related legislation and/or case law as may be or name Eril®. NOTE: the fasudil sold by LC Laboratories is NOT become applicable in the aforementioned countries; and (viii) such Eril® and is NOT for human use. similar laws and rules as may apply in various other countries. • Sold for laboratory or manufacturing purposes only; not for • Not available in some countries; not available to some institutions; human, medical, veterinary, food, or household use. not available for some uses.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 41 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

OH CH CH O by the trade names listed above under “related terms” and is NOT H C CH 3 3 3 3 for human use. N • Sold for laboratory or manufacturing purposes only; not for H human, medical, veterinary, food, or household use. CH 3 • This product is offered for R&D use in accordance with (i) 35 FHPI — see SB 202190 (Cat. No. S-1700 on page 102). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent FI-106 — see Doxorubicin, Hydrochloride Salt Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. (Cat. No. D-4000 on page 33). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) F-4633 Fingolimod, Hydrochloride Salt, >99% Section 68B of the Patents Act of 1953 in New Zealand together Synonyms: [FTY-720A] [FTY720] with the amendment of same by the Statutes Amendment Bill of Related: [Gienia] [Gilena] [Gilenya] 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such Size US$ ¤ £ ¥ similar laws and rules as may apply in various other countries. 100 mg 48 37 32 5,400 • Not available in some countries; not available to some institutions; 200 mg 87 67 58 9,700 not available for some uses. 300 mg 122 94 81 13,600 • Please see also our other standard immunosuppressant products: 500 mg 174 135 115 19,500 - Ascomycin (Cat. No. A-1040 on page 7) 1 g 232 179 153 25,900 - Cyclosporin A (Cat. No. C-6000 on page 25) 2 g 416 322 275 46,500 - Everolimus (Cat. No. E-4040 on page 40) 5 g 850 657 562 95,000 - FK-506 (Cat. No. F-4900 on page 42) NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. - Pimecrolimus (Cat. No. P-6040 on page 91) - Rapamycin (Cat. No. R-5000 on page 96) M.W. 343.93 c19H33NO2•HCl [162359-56-0] M.I. 14: 4083 - Temsirolimus (Cat. No. T-8040 on page 111) - Tofacitinib, Free Base (Cat. No. T-1377 on page 114) Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; - Zotarolimus, Free Base (Cat. No. Z-9040 on page 128) very poorly soluble in water. Up to 25 mL of a solution of . HCl 13.8 mg/mL (40 mM) fingolimod-HCl in 100% DMSO can HO be diluted into 5 mL of plain water without precipitation, HO giving a final concentration of 200 mM. In contrast, even a NH 1-to-1,000 dilution of the same 13.8 mg/mL DMSO stock 2 solution into a 10 mM phosphate-buffered saline at pH 7 results in a precipitate. Thus, fingolimod-HCl solubility in F-4900 FK-506, >99% PBS is likely to be well below 100 mM, perhaps as low as Synonyms: [FR-900506] [Tacrolimus] 1-10 mg/mL. Either DMSO, ethanol or plain water should be used as the solvent until the final dilution is made into Related Terms: [Fujimycin] [Prograf] culture medium. Buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A Size US$ ¤ £ ¥ 50 mg 67 52 44 7,500 • Fingolimod (FTY720), a sphingosine 1-phosphate (S1P) analog, 100 mg 119 92 79 13,300 is a novel immunosuppressant drug that induces lymphopenia by preventing emergence of lymphocytes from lymph nodes. 200 mg 175 135 116 19,600 Fingolimod is a sphingosine-1-phosphate receptor 1 modulator 500 mg 298 230 197 33,300 and is in phase III clinical trials for relapsing-remitting multiple 1 g 485 375 321 54,200 sclerosis. Chiba, K. et al., “Role of sphingosine 1-phosphate 2 g 896 693 592 100,200 receptor type 1 in lymphocyte egress from secondary lymphoid 5 g 1435 1109 949 160,400 tissues and thymus.” Cell Mol. Immunol. 3: 11-19 (2006). NOTE: Euro, Pound and Yen prices are revised regularly. Dev, K.K. et al., “Brain sphingosine-1-phosphate receptors: Please visit www.LCLabs.com for our current prices. implication for FTY720 in the treatment of multiple sclerosis.” M.W. 804.02 c44H69NO12 [104987-11-3] Pharmacol. Ther. 117: 77-93 (2008). M.I. 14: 9025 • Suppresses allotransplant rejections and autoimmune disorders in different animal models. Kunzendorf, U. et al., “FTY720—the Storage: Store at or below -20 °C. Solubility: Soluble in first compound of a new promising class of immunosuppressive DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; drugs.” Nephrol. Dial. Transplant. 19: 1677-1681 (2004). very poorly soluble in water; maximum solubility in plain water is estimated to be about 10 µM; buffers, serum, or • Fingolimod appears to promote the survival of human and animal other additives may increase or decrease the aqueous allografts by sequestering T lymphocytes within peripheral solubility. Disposal: A lymphoid tissue. Evidence for this mechanism of sequestration includes: (1) fingolimod drives T lymphocytes into peripheral • Ascomycin level is less than 0.5%. lymph nodes in a chemokine dependent manner; (2) fingolimod • Available in gram to kilogram quantities—request a bulk quote. downregulates sphingosine 1-phosphate receptors (S1PRs) on • FK-506 is a potent immunosuppressant and in vitro T cell the T lymphocyte surface, preventing it from migrating along proliferation blocker. It has been shown to disrupt calcineurin a S1P gradient; and (3) fingolimod blocks stromal gates on the (also known as phosphatase 2B)-mediated signal transduction in abluminal side of the lymphatic endothelium. Yopp, A.C. et al., T lymphocytes. The compound interacts with its FK-506-binding “Sphingosine 1-phosphate receptor modulators: a new class of protein-12 (FKBP-12). The resulting complex, in turn, interferes immunosuppressants.” Clin. Transplant. 20: 788-795 (2006). with calcineurin substrate interaction. Dumont, F.J., “FK-506, an • Fingolimod is the active ingredient in the drug products sold immunosuppressant targeting calcineurin function.” Curr. Med. under the trade name Gilena® and the other trade names listed Chem. 7: 731-748 (2000). above under “Related Terms”. NOTE: the fingolimod sold by LC • FK-506 inhibits FKBP activity resulting in an increase in the Laboratories is NOT Gilena® nor any other drug product specified release of sarcoplasmic reticulum-derived calcium. FK-506 also

42 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

appears to inhibit Na(+)-Ca2+ exchange. Prolonged exposure of Xenopus A6 cells to FK-506 significantly inhibits aldosterone- F-4185 Foretinib, Free Base, >99% stimulated Na+ transport and Na(+)-K(+)-ATPase activity. Unlike Synonyms: [Exel-2880] [GSK-1363089] [GSK089] rapamycin, which also binds to FK-506-binding protein-12, [XL-880] FKBP12 with or without bound FK-506 has no effect on rat brain PKC activity in vitro. McCall, E., “Effects of FK-506 on Size US$ ¤ £ ¥ contraction and Ca2+ transients in rat cardiac myocytes.” 5 mg 47 36 31 4,400 Circ. Res. 79: 1110-1121 (1996). Rokaw, M.D., et al “FK- 10 mg 63 48 42 5,900 506 and rapamycin but not cyclosporin inhibit aldosterone- 25 mg 131 101 87 12,300 stimulated sodium transport in A6 cells.” Am. J. Physiol. 50 mg 222 170 148 20,800 271: C194‑202 (1996). Rokaw, M.D. et al., “Rapamycin inhibits protein kinase C activity and stimulates Na+ transport in A6 cells.” 100 mg 389 299 259 36,400 J. Biol. Chem. 271: 32468-32473 (1996). 200 mg 735 564 489 68,800 • The CAS number for the anhydrous form of FK-506 is given 500 mg 1680 1290 1117 157,200 NOTE: Euro, Pound and Yen prices are revised regularly. above. The CAS number for FK-506 monohydrate is 109581‑93‑3. Please visit www.LCLabs.com for our current prices. • FK-506 (Tacrolimus) is the active ingredient in the drugs sold M.W. 632.65 c H F N O [849217-64-7] under the trade names Fujimycin® and Prograf®. NOTE: the FK- 34 34 2 4 6 506 (Tacrolimus) sold by LC Laboratories is NOT Fujimycin® nor Storage: Store at or below -20 ºC. Solubility: Soluble in Prograf® and is NOT for human use. DMSO at 150 mg/mL; soluble in ethanol at 5 mg/mL with • Sold for laboratory or manufacturing purposes only; not for warming; very poorly soluble in water; maximum solubility human, medical, veterinary, food, or household use. in plain water is estimated to be about 5-10 µM; buffers, serum, or other additives may increase or decrease the • This product is offered for R&D use in accordance with (i) 35 aqueous solubility. Disposal: A USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Foretinib, also known as EXEL-2880, XL880, and GSK1363089, Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. is a small-molecule inhibitor of the hepatocyte growth factor Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) (HGF) and vascular endothelial growth factor (VEGF) receptor and other common law exemptions of Canadian patent law; (vi) tyrosine kinase families. Section 68B of the Patents Act of 1953 in New Zealand together • Foretinib inhibited receptor tyrosine kinases (RTKs) in vitro with with the amendment of same by the Statutes Amendment Bill of IC50 values of 0.4 nM for Met and 3 nM for Ron. It inhibited 2002; (vii) such related legislation and/or case law as may be or cellular Met with IC50 values of 23 nM in PC-3 prostate cells become applicable in the aforementioned countries; and (viii) such and 21 nM in murine B16F10 melanoma cells. It also reduced similar laws and rules as may apply in various other countries. tumor cell migration, invasion, and endothelial tubule formation. • Not available in some countries; not available to some institutions; Foretinib had cytotoxic activities against a broad panel of cell not available for some uses. lines. It also blocked lung metastasis after the implantation of B16F10 solid tumors in mice. Qian, F. et al., “Inhibition of tumor • See also our other standard immunosuppresent products: cell growth, invasion, and metastasis by EXEL-2880 (XL880, - Ascomycin (Cat. No. A-1040 on page 7) GSK1363089), a novel inhibitor of HGF and VEGF receptor - Cyclosporin (Cat. No. C-6000 on page 25) tyrosine kinases.” Cancer Res. 69: 8009‑8016 (2009). - Everolimus (Cat. No. E-4040 on page 40) • MET-amplified tumor lines with HER1 or HER2 amplification - Pimecrolimus (Cat. No. P-6040 on page 91) are more sensitive to the combination of foretinib with lapatinib - Rapamycin (Cat. No. R-5000 on page 96) or erlotinib. MET-overexpressing tumor cell lines with HER1 or HER2 amplification are less sensitive to lapatinib or erlotinib - Temsirolimus (Cat. No. T-8040 on page 111) in the presence of HGF. Foretinib can reverse the effect of HGF - Zotarolimus, Free Base (Cat. No. Z-9040 on page 128) on lapatinib or erlotinib sensitivity in these cells. Liu, L. et al., “Synergistic effects of foretinib with HER-targeted agents in MET HO and HER1- or HER2-coactivated tumor cells.” Mol. Cancer Ther. 10: 518‑530 (2011). H CO CH 3 3 • Foretinib inhibits tumorigenesis and blocks invasive tumor growth H C O 3 CH in different models of ovarian cancer by affecting several critical 2 tumor functions including inducing anoikis (anchorage-dependent O OH programmed cell death) and inhibiting (1) c-Met activation N O and downstream signaling, (2) ovarian cancer cell adhesion, O CH O 3 (3) migration and invasion, and (4) proliferation. Zillhardt, M. OH et al., “Foretinib (GSK1363089), an orally available multikinase H C CH 3 O 3 inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis.” Clin. Cancer Res.

OCH 17: 4042‑4051 (2011). 3 OCH 3 • Foretinib potently block multiple RTKs, including VEGF receptor and the receptor of HGF c-Met. Inhibition of c-Met FK-520 — see Ascomycin (Cat. No. A-1040 on page 7). and functionally related kinases intensifies the effects of Flavo — see Alvocidib, Free Base (Cat. No. A-3465 on page 6). VEGF receptor blockade, which leads to regression of tumor vasculature. You, W.K. et al., “VEGF and c-Met blockade amplify Flavopiridol — see Alvocidib, Free Base (Cat. No. A-3465 on page 6). angiogenesis inhibition in pancreatic islet cancer.” Cancer Res. 4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole 71: 4758‑4768 (2011). — see SB 202190 (Cat. No. S-1700 on page 102). • Foretinib caused mitotic catastrophe in chronic myelogenous leukemia cells and other cell lines by JNK-dependent inhibition of 4-(4'‑Fluorophenyl)-2-(4'-methylsulfinylphenyl)-5-(4'-pyridyl) Plk1 expression and induced apoptosis via a caspase 2-mediated imidazole — see SB 203580 (Cat. No. S-3400 on page 103). mechanism. Dufies, M. et al., “Mechanism of action of the Foloxatine — see Oxaliplatin (Cat. No. O-7111 on page 79). multikinase inhibitor Foretinib.” Cell Cycle 10: 4138‑4148 (2011). • Foretinib had cytotoxic effects against gastric cancer cells harboring MET and FGFR2 amplification. It exerted its cytotoxic effects by blocking inter-RTK signaling networks with

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 43 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

MET or FGFR2 at their center. Kataoka, Y. et al., “Foretinib and Karaki, H.J., “Effect of forskolin on cytosolic Ca++ level and (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, contraction in vascular smooth muscle.” J. Pharmacol. Exp. Ther. inhibits growth of gastric cancer cell lines by blocking inter- 249: 895-900 (1989). receptor tyrosine kinase networks.” Invest. New Drugs • Forskolin is an inhibitor of mammalian glucose transporters 30: 1352‑1360 (2012). and of a bacterial galactose-H+ transporter, GalP. Joost, H.G. • Foretinib was shown to have significant antitumor activities and Steinfelder, H.J., “Forskolin inhibits insulin-stimulated in patient-derived hepatocellular carcinoma xenograft models. glucose transport in rat adipose cells by a direct interaction Huynh, H. et al., “Foretinib demonstrates anti-tumor activity and with the glucose transporter.” Mol. Pharmacol. 31: 279 improves overall survival in preclinical models of hepatocellular (1987). Martin, G.E. et al., “Forskolin specifically inhibits the carcinoma.” Angiogenesis 15: 59‑70 (2012). bacterial galactose-H+ transport protein, GalP.” J. Biol. Chem. • Another CAS number previously assigned to foretinib free base, 269: 24870‑24877 (1994). namely 937176-80-2, has been deleted by CAS and is no longer in • Forskolin blocks PKC-activated ERK1 and ERK2 tyrosine use. phosphorylation and inhibits PKC-stimulated MAPK and Raf-1 • Sold for laboratory or manufacturing purposes only; not for activities in mouse bone-forming cells (MC3T3-E1 osteoblasts). human, veterinary, food, or household use. Siddhanti, S.R. et al., “Forskolin inhibits protein kinase C-induced mitogen activated protein kinase activity in MC3T3-E1 • This product is offered for R&D use in accordance with (i) 35 osteoblasts.” Endocrinology. 136: 4834-4841 (1995). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Sold for laboratory or manufacturing purposes only; not for Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. human, medical, veterinary, food, or household use. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) O and other common law exemptions of Canadian patent law; (vi) HO Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of O 2002; (vii) such related legislation and/or case law as may be or H OH become applicable in the aforementioned countries; and (viii) such O similar laws and rules as may apply in various other countries. OH • Not available in some countries; not available to some institutions; O not available for some uses. FR-900506 — see FK-506 (Cat. No. F-4900 on page 42). H H FR-900520 — see Ascomycin (Cat. No. A-1040 on page 7). F N N FTY-720A — see Fingolimod, Hydrochloride Salt O O CH O F (Cat. No. F-4633 on page 42). 3 O FTY720 — see Fingolimod, Hydrochloride Salt (Cat. No. F-4633 on page 42). N O N Fujimycin — see its active ingredient, namely FK-506 O (Cat. No. F-4900 on page 42). Gamcitabine — see Gemcitabine, Free Base (Cat. No. G-4199 F-9929 Forskolin, >99% on page 46) and its active ingredient, namely Gemcitabine, [Colforsin] Hydrochloride Salt (Cat. No. G-4177 on page 47).

Size US$ ¤ £ ¥ GDC-0449 — see Vismodegib, Free Base (Cat. No. V-4050 on page 121). 50 mg 77 57 48 7,500 100 mg 132 97 82 12,900 G-9252 GDC-0941, Free Base, >99% 300 mg 325 240 203 31,700 New Generic Name: [Pictilisib] 1 g 660 487 412 64,300 2 g 1146 845 716 111,700 Size US$ ¤ £ ¥ 5 g 2375 1752 1483 231,500 25 mg 42 32 28 4,700 NOTE: Euro, Pound and Yen prices are revised regularly. 50 mg 76 59 50 8,500 Please visit www.LCLabs.com for our current prices. 100 mg 129 100 85 14,400 M.W. 410.50 c22H34O7 [66575-29-9] 200 mg 217 168 143 24,300 M.I. 14: 2476 500 mg 495 383 327 55,300 Storage: Store at or below -20 °C. Solubility: Soluble in 1 g 865 669 572 96,700 DMSO at 160 mg/mL; soluble in ethanol at 50 mg/mL; 2 g 1590 1229 1051 177,800 very poorly soluble in water; maximum solubility in plain NOTE: Euro, Pound and Yen prices are revised regularly. water is estimated to be about 25-50 µM; buffers, serum, Please visit www.LCLabs.com for our current prices. or other additives may increase or decrease the aqueous M.W. 513.64 c H N O S [957054-30-7] solubility. Disposal: A 23 27 7 3 2 Storage: Store at or below -20 ºC. Solubility: Soluble in • Forskolin is a naturally occurring diterpene from the Indian DMSO at 66 mg/mL; very poorly soluble in ethanol; very plant, Coleus forskohlii, that works as an activator of adenylate poorly soluble in water; maximum solubility in plain water cyclase resulting in an increase in the intracellular concentration is estimated to be about 10-50 µM; buffers, serum, or of cAMP. Laurenza, A. et al., “Forskolin: a specific stimulator other additives may increase or decrease the aqueous of adenylyl cyclase or a diterpene with multiple sites of action?” solubility. Disposal: A Trends Pharm. Sci. 10: 442-447 (1989). Barber, R. and Goka, T.J., “Adenylate cyclase activity as a function of forskolin • GDC-0941 is a phosphatidylinositol 3-kinase (PI3K) inhibitor. concentration.” J. Cyclic Nucleotide Protein Phosphor. Res. Folkes, A.J. et al., “The identification of 2-(1H-indazol-4-yl)- 10: 23‑29 (1985). 6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl- thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally • Forskolin acts as a smooth muscle relaxant and vasodilator in a bioavailable inhibitor of class I PI3 kinase for the treatment of concentration-dependent manner that affects both cytoplasmic cancer.” J. Med. Chem. 51: 5522-5532 (2008). calcium levels and contractile element calcium sensitivity. Abe, A.

44 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• GDC-0941 inhibited the growth of >70% of breast cancer cell G-4408 Gefitinib, Free Base, >99% lines tested, with EC50’s <1 µM. GDC-0941 also demonstrated antitumor activity in preclinical models of breast cancer. Yao, [Iressa] [ZD1839] E. et al., “Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K Size US$ ¤ £ ¥ inhibitor, trastuzumab, and pertuzumab.” Clin. Cancer Res. 1 g 77 59 51 7,300 15: 4147‑4156 (2009). 2 g 132 102 87 12,500 • The combination of GDC-0941 with trastuzumab is highly 5 g 215 166 141 20,300 efficacious in the treatment of cancer cells in vitro and tumors 10 g 355 273 233 33,600 in vivo. GDC-0941 also has antitumor activity in the treatment 25 g 775 597 509 73,200 of trastuzumab-resistant cells and tumors. Junttila, T.T. et al., 100 g 2250 1733 1477 212,600 “Ligand-independent HER2/HER3/PI3K complex is disrupted NOTE: Euro, Pound and Yen prices are revised regularly. by trastuzumab and is effectively inhibited by the PI3K inhibitor Please visit www.LCLabs.com for our current prices. GDC-0941.” Cancer Cell 15: 429-440 (2009). M.W. 446.90 c H ClFN O [184475-35-2] • GDC-0941 inhibits the activity of recombinant PI3K in vitro 22 24 4 3 Storage: Store at or below -20 °C. Solubility: Soluble in with IC50’s of 0.003 µM (P110a), 0.033 µM (P110b), 0.003 µM (P110d), 0.075 µM (P110g), 0.58 µM (mTOR) and 1.23 µM DMSO, up to about 100 mg/mL; very poorly soluble in (DNA-PK). GDC-0941 inhibited the growth of tumor cells in water or ethanol. Disposal: A vitro with IC50’s of 0.95 µM (U87MG), 0.07 µM (IGROV-1), 0.15 • Gefitinib inhibits EGFR tyrosine kinase by binding to the µM (DETROIT 562), 0.28 µM (PC3) and 0.54 µM (SKOV-3). adenosine triphosphate (ATP)-binding site of the enzyme. Thus GDC-0941 also inhibited the growth of U87 MG glioblastoma the function of the EGFR tyrosine kinase in activating the Ras xenografts and IGROV-1 ovarian cancer xenografts in mice. signal transduction cascade is inhibited, and malignant cell growth Raynaud, F.I. et al., “Biological properties of potent inhibitors is inhibited. Research on gefitinib-sensitive non-small cell lung of class I phosphatidylinositide 3-kinases: from PI-103 through cancers has shown that a mutation in the EGFR tyrosine kinase PI-540, PI-620 to the oral agent GDC-0941.” Mol. Cancer Ther. domain is responsible for activating anti-apoptotic pathways. 8: 1725‑1738 (2009). These mutations tend to confer increased sensitivity to tyrosine • A CAS number previously in use for this compound, 1146702-55- kinase inhibitors such as gefitinib and erlotinib. Of the types of 7, has been deleted by Chemical Abstracts Service. non-small cell lung cancer histologies, adenocarcinoma is the type • Sold for laboratory or manufacturing purposes only; not for that most often harbors these mutations. These mutations are more human, medical, veterinary, food, or household use. commonly seen in Asians, women, and non-smokers (who also tend to more often have adenocarcinoma). Pao W. et al., “EGF • This product is offered for R&D use in accordance with (i) 35 receptor gene mutations are common in lung cancers from “never USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese smokers” and are associated with sensitivity of tumors to gefitinib Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent and erlotinib.” Proc. Natl. Acad. Sci. USA 101: 13306-13311 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. (2004). Sordella R. et al., “Gefitinib-sensitizing EGFR mutations Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) in lung cancer activate anti-apoptotic pathways.” Science and other common law exemptions of Canadian patent law; (vi) 305: 1163‑1167 (2004). Section 68B of the Patents Act of 1953 in New Zealand together • The IC values for gefitinib for inhibiting HT-29 and LoVo cell with the amendment of same by the Statutes Amendment Bill of 50 2002; (vii) such related legislation and/or case law as may be or growth were 23.6->100 µM and 7.3-48.5 µM, respectively, when become applicable in the aforementioned countries; and (viii) such the exposure times are from 18 hours to 3 days. A time-dependent reduction in IC was observed for gefitinib, with the IC after similar laws and rules as may apply in various other countries. 50 50 3 days of exposure being 4-8 times lower than after 18 hours • Not available in some countries; not available to some institutions; of exposure. Azzariti A. et al., “Prolonged exposure of colon not available for some uses. cancer cells to the epidermal growth factor receptor inhibitor O gefitinib (Iressa™) and to the antiangiogenic agent ZD6474: Cytotoxic and biomolecular effects.” World J. Gastroenterol. 12: 5140‑5147 (2006). N • Found to be a potent inhibitor of EGFR kinase (Ki = 0.40 nM), but S N N much weaker against ErbB-2 kinase (Ki = 870 nM) and ErbB- NH 4 kinase (Ki =1.1 µM). Wood E.R. et al., “A Unique Structure N N for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib), Relationships among Protein Conformation, Inhibitor N Off-Rate, and Receptor Activity in Tumor Cells.” O S Cancer Res. 64: 6652-6659 (2004). H C O 3 • Selectivity was demonstrated by the >100-fold difference in IC50

for cells grown in the presence (IC50 = 0.054 µM) or absence

(IC50 = 8.8 µM) of EGF. Similarly, gefitinib selectively inhibited EGF-stimulated growth of HUVECs compared with FGF- or VEGF-stimulated growth. Enzyme kinetic studies to determine the characteristics of gefitinib inhibition of EGFR TK, in which peptide substrate concentration was fixed at 2 mM (~6-fold higher

than the Km) and the ATP concentration was varied, showed that

gefitinib is a competitive inhibitor with respect to ATP (Ki = 2.1 nM). Similarly, when the ATP concentration was fixed at 50

µM (~6-fold higher than the Km) and peptide concentration was

varied, gefitinib showed noncompetitive kinetics (Ki = 15.0 nM). Wakeling A.E. et al., “ZD1839 (Iressa), An Orally Active Inhibitor of Epidermal Growth Factor Signaling with Potential for Cancer Therapy.” Cancer Res. 62: 5749-5754 (2002). • Gefitinib is the active ingredient in the drug sold under the trade name Iressa®. The drug is approved in at least one country for the treatment of locally advanced or metastatic non-small cell lung

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 45 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

cancer in patients who have previously received chemotherapy. • For very similar but much more stable geldanamycin analogs, NOTE: the gefitinib sold by LC Laboratories is NOT Iressa® and please see: is NOT for human use. - 17-AAG (Cat. No. A-6880 on page 1). • Sold for laboratory or manufacturing purposes only; not for - 17-DMAG, Hydrochloride Salt (Cat. No. D-3440 on page 28). human, medical, veterinary, food, or household use. • Sold for laboratory or manufacturing purposes only; not for • This product is offered for R&D use in accordance with (i) 35 human, medical, veterinary, food, or household use. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent O H C O Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 3 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) O CH 3 and other common law exemptions of Canadian patent law; (vi) NH

Section 68B of the Patents Act of 1953 in New Zealand together O with the amendment of same by the Statutes Amendment Bill of H C 3 H H C O 2002; (vii) such related legislation and/or case law as may be or O 3 H C O CH become applicable in the aforementioned countries; and (viii) such 3 3 similar laws and rules as may apply in various other countries. H C 3 • Not available in some countries; not available to some institutions; OCONH not available for some uses. 2

O N Geldanomycin – see Geldanamycin (Cat. No. G-4500 on page 46).

N G-4199 Gemcitabine, Free Base, >99% N O Synonyms: [dFdC] [LY-188011] O NH Cl Related Terms: [Gamcitabine] [Gemcitera] [Gemsar]

F [Gemzar] [Zefei] Size US$ ¤ £ ¥ G-4500 Geldanamycin, >99% 100 mg 43 31 26 5,200 [Geldanomycin] [U-29135] 300 mg 87 63 52 10,600 Size US$ ¤ £ ¥ 500 mg 119 86 71 14,500 25 mg 67 52 44 7,500 1 g 222 160 132 27,000 50 mg 85 66 56 9,500 2 g 366 265 218 44,600 100 mg 118 91 78 13,200 5 g 575 416 342 70,000 250 mg 198 153 131 22,100 10 g 880 636 524 107,200 1 g 422 326 279 47,200 25 g 1375 994 818 167,500 NOTE: Euro, Pound and Yen prices are revised regularly. 2 g 740 572 489 82,700 Please visit www.LCLabs.com for our current prices. 5 g 1290 997 853 144,200 M.W. 263.20 c H F N O [95058-81-4] 10 g 1980 1531 1309 221,400 9 11 2 3 4 M.I. 14: 4386 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 ºC. Solubility: Soluble in M.W. 560.64 c H N O [30562-34-6] DMSO at 65 mg/mL; soluble in ethanol at 12 mg/mL with 29 40 2 9 slight warming; soluble in water at 15 mg/mL with slight Warning: Toxic. warming; buffers, serum, or other additives may increase Storage: Store at or below -20 ºC. Solubility: Soluble in or decrease the aqueous solubility. Disposal: A DMSO at 100 mg/mL; see further information below for • This is the free base form of gemcitabine; please see the stability and solubility in other solvents. Disposal: A other form of this product, Gemcitabine, Hydrochloride Salt • Binds specifically to heat shock protein HSP90 and its GP96 (Cat. No. G‑4177 on page 47), for further technical information. The homologue; inhibits protein maturation. Whitesell, L. and Cook, hydrochloride salt form is used for some or all of the formulations P., “Stable and specific binding of heat shock protein 90 by of gemcitabine for in vivo use. geldanamycin disrupts glucocorticoid receptor function in intact • Gemcitabine (as the hydrochloride salt) is the active ingredient in cells.” Mol. Endocr. 10: 705-712 (1996). drug products sold under numerous trade names as listed near the • Stability: Geldanamycin’s methoxy group on the quinone ring top of this product entry as “Related Terms”. These drugs products is reactive — it can be displaced by other alcohols or water. have been approved in at least one country to be used alone or in Thus, geldanamycin is unstable in water and ethanol, and those combination with other medicines to treat breast cancer, ovarian solvents should not be used for making stock solutions. Although cancer, non-small cell lung cancer, and cancer of the pancreas. geldanamycin stability in methanol would not be a problem NOTE: THE GEMCITABINE, Free Base RESEARCH (because no structural change occurs if the geldanamycin reacts COMPOUND SOLD BY LC LABORATORIES IS NOT any with methanol — it is just a methoxy interchange), solubility in of the Gemcitabine-containing drug products methanol is very poor. DMSO itself probably does not react with sold under various trade names and is not for geldanamycin, but DMSO can contain moisture from the air and/ human use. or small amounts of DMSO degradation products that might react • NOTE: the trade names listed above under “Related Terms” are for with geldanamycin. Thus, DMSO stock solutions should be kept gemcitabine-containing drug products and may apply variously to out of contact with air to the greatest extent possible. formulations of one or another form of gemcitabine, such as the • Solubility in Water: Geldanamycin is very poorly soluble in water; free base, hydrochloride salt or other salt form. maximum solubility in plain water is estimated to be about 20-50 • This gemcitabine product is the free base, whose CAS number µM; buffers, serum or other additives may increase or decrease the is given above. The CAS number of the hydrochloride salt is aqueous solubility. Although geldanamycin is somewhat unstable 122111-03-9. in water, it is of course unavoidable that biological testing of • Another CAS number previously assigned to gemcitabine free geldanamycin will expose the compound to water. We do not have base, namely 1239668-67-7, has been deleted by CAS and is no any data on the actual rate of geldanamycin decomposition in longer in use. water or other aqueous media.

46 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Sold for laboratory or manufacturing purposes only; not for • Gemcitabine inhibited DNA synthesis in a concentration- human, veterinary, food, or household use. dependent manner in human lymphoblastoid CEM cells. The • This product is offered for R&D use in accordance with (i) 35 apparent Ki values of gemcitabine triphosphate (dFdCTP) were USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 11.2 µM for DNA polymerase α and 14.4 µM for polymerase ε. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Huang P. et al., “Action of 2',2'-difluorodeoxycytidine on DNA Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. synthesis.” Cancer Res. 51: 6110-6117 (1991). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • Gemcitabine inhibited DNA synthesis. However, the cytotoxicity and other common law exemptions of Canadian patent law; (vi) of gemcitabine on proliferating cells was not specific for cells Section 68B of the Patents Act of 1953 in New Zealand together initially in S phase. The kinetics of cell recycling from a first with the amendment of same by the Statutes Amendment Bill of gemcitabine treatment have a strong effect on the outcome of 2002; (vii) such related legislation and/or case law as may be or a second treatment with either gemcitabine itself or cisplatin. become applicable in the aforementioned countries; and (viii) such Cappella P. et al., “Cell cycle effects of gemcitabine.” similar laws and rules as may apply in various other countries. Int. J. Cancer 93: 401-408 (2001). • Not available in some countries; not available to some institutions; • Gemcitabine increases DNA ligase I levels severalfold in different not available for some uses. types of tumor cell lines, including MiaPaCa, NGP and SK-N-BE.

NH However, DNA ligases III and IV either remained unchanged or 2 decreased with treatment. Sun D. et al., “Enhancement of DNA N ligase I level by gemcitabine in human cancer cells.” Clin. Cancer Res. 8: 1189-1195 (2002). O N • Gemcitabine Hydrochloride is the active ingredient in drug F products sold under numerous trade names as listed near the top O F of this product entry as “Related Terms”. These drugs products

HO have been approved in at least one country to be used alone or in OH combination with other medicines to treat breast cancer, ovarian cancer, non-small cell lung cancer, and cancer of the pancreas. G-4177 Gemcitabine, Hydrochloride Salt, >99% NOTE: THE GEMCITABINE HYDROCHLORIDE RESEARCH Synonyms: [dFdC] [LY-188011] COMPOUND SOLD BY LC LABORATORIES IS NOT any Related Terms: [Gamcitabine] [Gemcitera] [Gemsar] of the Gemcitabine-containing drug products [Gemzar] [Zefei] sold under various trade names and is not for human use. Size US$ ¤ £ ¥ • Our gemcitabine product is the hydrochloride salt, whose CAS 100 mg 43 31 26 5,200 number is given above. The CAS number of the free base is 300 mg 87 63 52 10,600 95058-81-4. 500 mg 119 86 71 14,500 • We note that one of our competitors, Active Biochem, as of July 1 g 222 160 132 27,000 13, 2011, is claiming 100% purity for its Gemcitabine, Free Base. This claim is not credible because it is physically impossible. 2 g 366 265 218 44,600 5 g 575 416 342 70,000 • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. 10 g 880 636 524 107,200 25 g 1375 994 818 167,500 • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. M.W. 299.66 c H F N O •HCl [122111-03-9] 9 11 2 3 4 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Storage: Store at or below -20 °C. Solubility: Soluble in and other common law exemptions of Canadian patent law; (vi) DMSO at 12.5 mg/mL with slight warming; very poorly Section 68B of the Patents Act of 1953 in New Zealand together soluble in ethanol; soluble in water at 25 mg/mL with slight with the amendment of same by the Statutes Amendment Bill of warming; buffers, serum, or other additives may increase 2002; (vii) such related legislation and/or case law as may be or or decrease the aqueous solubility. Disposal: A become applicable in the aforementioned countries; and (viii) such • Gemcitabine is a nucleoside analog of deoxycytidine used as similar laws and rules as may apply in various other countries. chemotherapy to treat patients with various types of cancer. • Not available in some countries; not available to some institutions; • After passage through the cell membrane via nucleoside not available for some uses. transporters, gemcitabine undergoes complex intracellular NH2 conversion to gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP). dFdCTP inhibits DNA polymerase by N competing with deoxycytidine triphosphate (dCTP). dFdCDP • HCl inhibits ribonucleoside reductase and DNA synthesis by causing O N depletion of deoxyribonucleotide pools, and thus potentiating F the effects of dFdCTP. Gemcitabine can be inactivated to O F 2,2'-difluorodeoxyuridine, mainly by deoxycytidine deaminase. G-4177-2010-04-03-tdr-CD-rev.eps Also, 5'-nucleotidase catalyses the conversion of nucleotides HO OH to nucleosides and inhibits nucleoside kinases. Mini E., et al., “Cellular pharmacology of gemcitabine.” Ann. Oncol. Gemcitera – see Gemcitabine, Free Base (Cat. No. G-4199 on page 46) and its active ingredient, namely Gemcitabine, 17: v7‑12 (2006). Hydrochloride Salt (Cat. No. G-4177 on page 47). • Gemcitabine remains the current standard of care for pancreatic cancer as a single agent. Combinations with biological agents or Gemsar – see Gemcitabine, Free Base (Cat. No. G-4199 on page 46) other chemotherapeutic drugs (including capecitabine, platinum and its active ingredient, namely Gemcitabine, Hydrochloride compounds, erlotinib, and monoclonal antibodies cetuximab Salt (Cat. No. G-4177 on page 47). and bevacizumab) have shown limited improvement. Cartwright Gemzar – see Gemcitabine, Free Base (Cat. No. G-4199 on page 46) T., et al., “Cancer of the pancreas: are we making progress? and its active ingredient, namely Gemcitabine, Hydrochloride A review of studies in the US Oncology Research Network.” Salt (Cat. No. G-4177 on page 47). Cancer Control 15: 308-313 (2008).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 47 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

The Soybean Isoflavone Family G-6055 Genistein, >99% Numbers Twelve Members [4',5,7-Trihydroxyisoflavone] The presence in soybeans of genistein and its glucoside, genistin, has been recognized for many decades. For much of that time it was believed Size US$ ¤ £ ¥ that the primary form of this isoflavone in unprocessed soybeans was the 1 g 59 46 39 6,600 glucoside form, genistin. Similarly, daidzin and its aglycone daidzein have 5 g 152 117 100 17,000 long been known as soy constituents. 10 g 245 189 162 27,400 There is now a large literature describing the biological properties of 25 g 445 344 294 49,800 genistein in particular, because of its activity as a tyrosine kinase inhibi- 50 g 785 607 519 87,800 tor, as a possible anti-oxidant and as a potential anti-cancer compound, 100 g 1175 908 777 131,400 among other notable discoveries. Over the years much has also been NOTE: Euro, Pound and Yen prices are revised regularly. published regarding the interesting and potentially useful activities of Please visit www.LCLabs.com for our current prices. daidzein and daidzin. M.W. 270.24 C15H10O5 [446-72-0] More recently, another glucoside/aglycone pair, namely glycitin and M.I. 14: 4391 glycitein respectively, were identified in soy extracts. Because of the Storage: Store at or below -20 °C. Solubility: Soluble in reatively low levels of glycitin and glycitein in soy products and attendant DMSO at 200 mg/mL; soluble in ethanol at 8 mg/mL with lack of affordable material for experimental use, their biological properties warming; very poorly soluble in water; maximum solubility have remained largely a mystery in spite of their potential importance. in plain water is estimated to be about 50-100 µM; buffers, LC Laboratories® is pleased to make available all six of these glucosides serum, or other additives may increase or decrease the and aglycones at reasonable prices. aqueous solubility. Disposal: A The story does not stop here, however. Research in the last few years • Tyrosine kinase inhibitor. Akiyama, T. et al., J. Biol. Chem. has turned up the surprising fact that a large, and often the predominant, 262: 5592‑5595 (1987). fraction of the isoflavones found in soybeans occurs not as the glucoside • See the extensive comments before the listing for Genistein forms but rather as their 6"-O-malonyl esters. Chemically, these compounds (Cat. No. G-6055 on page 48). consist of the glucoside form esterified with a single malonate half-ester, • Please request Technical Note #22 for additional information. located at the primary (6"-) hydroxy group of the sugar moiety. • Isoflavone derivative found in soy-based food products. Wang, This remarkable development has introduced major new uncertainties H. and Murphy, P.A., “Isoflavone content in commercial soybean as to the pharmacologically active components of soy products. Moreover, foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). further complicating matters, the malonyl esters are thermally and chemi- cally unstable and are easily converted during soy product processing to • See also these related products: either the free glucoside form or to yet another type of isoflavone derivative, - 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2). namely the 6"-O-acetyl esters, which are much more stable. - 6"-O-Acetylgenistin (Cat. No. A-3000 on page 3). As a result, the isoflavone fractions of soy products typically contain, - 6"-O-Acetylglycitin (Cat. No. A-7860 on page 3). in varying proportions, the entire twelve-compound isoflavone ensemble - Daidzein (Cat. No. D-2946 on page 26). – the malonyl glucosides of genistein, daidzein and glycitein; their ace- - Daidzin (Cat. No. D-7878 on page 26). tyl glucosides, their free glucosides and the free aglycones. Wang and Murphy [J. Agric. Food Chem. 42: 1666-1673 (1994)] have published an - (R,S)-Equol (Cat. No. E-5880 on page 37). analytical method for the simultaneous analysis of all twelve compounds - Genistin (Cat. No. G-5200 on page 49). and extensive data on their levels in a wide variety of soy-based products. - Glycitein (Cat. No. G-1152 on page 49). With these new developments, soy isoflavone research is entering a - Glycitin (Cat. No. G-2822 on page 50). new era, and LC Laboratories® is pleased to be able to offer all twelve - 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). members of this biologically, nutritionally and medically important family - 6"-O-Malonylgenistin (Cat. No. M-8090 on page 67). of compounds. (Please see individual catalog entries; bulk quantities are available for all twelve products.) - 6"-O-Malonylglycitin (Cat. No. M-4620 on page 68). • A catalog containing just these 14 products can be viewed and printed from our website, www.lclabs.com. Genfatinib – see its active ingredient, namely • Shipping charges for the 100 g size are slightly higher than our Imatinib, Free Base (Cat. No. I-5577 on page 53) and Imatinib, normal rates. Methanesulfonate Salt (Cat. No. I-5508 on page 54). • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.

OH OH O

HO O

Genistein, 7-O-b-d-glucopyranoside – see Genistin (Cat. No. G-5200 on page 49).

48 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

G-5200 Genistin, >99% G-1152 Glycitein, >99% [Genistein, 7-O-β-d-glucopyranoside] [4',7-Dihydroxy-6-methoxyisoflavone] Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 25 mg 56 43 35 4,700 5 mg 39 30 26 4,400 50 mg 83 63 51 6,900 10 mg 68 53 45 7,600 100 mg 129 98 80 10,800 25 mg 132 102 87 14,800 300 mg 198 150 122 16,500 50 mg 230 178 152 25,700 500 mg 299 227 185 25,000 100 mg 342 264 226 38,200 1 g 392 298 242 32,700 250 mg 590 456 390 66,000 2 g 760 578 470 63,500 500 mg 835 645 552 93,400 5 g 1670 1269 1033 139,400 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. M.W. 284.26 c16H12O5 [40957-83-3] M.W. 432.38 c21H20O10 [529-59-9] Storage: Store at or below -20 °C. Solubility: Soluble in M.I. 14: 4391 DMSO at 20 mg/mL with warming; very poorly soluble in Storage: Store at or below -20 °C. Solubility: Soluble in ethanol; very poorly soluble in water; maximum solubility DMSO at 100 mg/mL; very poorly soluble in ethanol; very in plain water is estimated to be about 1-2 µM; buffers, poorly soluble in water; maximum solubility in plain water serum, or other additives may increase or decrease the is estimated to be about 100-200 µM; buffers, serum, or aqueous solubility. Disposal: A other additives may increase or decrease the aqueous Note: this highly purified glycitein is very insoluble solubility. Disposal: A in mixtures of water with methanol, ethanol or • Isoflavone derivative found in soy-based food products. Wang, acetonitrile; with heating, a solution of 100 µg/mL H. and Murphy, P.A., “Isoflavone content in commercial soybean can be made, but upon cooling most of the glycitein foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). crystallizes out, leaving about 10 µg/mL or less in solution. • See the extensive comments before the listing for Genistein (Cat. No. G-6055 on page 48). • Isoflavone derivative found in soy-based food products. Wang, H. and Murphy, P.A., “Isoflavone content in commercial soybean • See also these related products: foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). - 6"-O-Acetylgenistin (Cat. No. A-3000 on page 3). • See the extensive comments before the entry for Genistein - Genistein (Cat. No. G-6055 on page 48). (Cat. No. G-6055 on page 48). - 6"-O-Malonylgenistin (Cat. No. M-8090 on page 67). • LC Laboratories® is pleased to be the first source of glycitein at • Sold for laboratory or manufacturing purposes only; not for prices low enough for routine study of this important dietary soy human, medical, veterinary, food, or household use. constituent.

OH • See also these related products: OH O - 6"-O-Acetylglycitin (Cat. No. A-7860 on page 3). OH - Glycitin (Cat. No. G-2822 on page 50). - 6"-O-Malonylglycitin (Cat. No. M-4620 on page 68). O O O • Sold for laboratory or manufacturing purposes only; not for OH HO human, medical, veterinary, food, or household use. HO OH O Genistin 6''-O-Acetate – see 6"-O-Acetylgenistin MeO (Cat. No. A-3000 on page 3).

Genistin 6''-O-Malonate – see 6"-O-Malonylgenistin, Free Acid HO O (Cat. No. M-8090 on page 67). Gienia – see its active ingredient, namely Fingolimod, Hydrochloride Salt (Cat. No. F-4633 on page 42). Gilena – see its active ingredient, namely Fingolimod, Hydrochloride Salt (Cat. No. F-4633 on page 42). Gilenya – see its active ingredient, namely Fingolimod, Hydrochloride Salt (Cat. No. F-4633 on page 42). Gilotrif – see its active ingredient, namely Afatinib, Free Base (Cat. No. A-8644 on page 4). Giotrif – see its active ingredient, namely Afatinib, Free Base (Cat. No. A-8644 on page 4). Glamox – see its active ingredient, namely Imatinib, Free Base (Cat. No. I-5577 on page 53). Gleevec – see its active ingredient, namely Imatinib, Free Base (Cat. No. I-5577 on page 53) and Imatinib, Methanesulfonate Salt (Cat. No. I-5508 on page 54). Glivec – see its active ingredient, namely Imatinib, Free Base (Cat. No. I-5577 on page 53) and Imatinib, Methanesulfonate Salt (Cat. No. I-5508 on page 54).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 49 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

G-2822 Glycitin, >99% G-6203 Gö 6976, >99% [Glycitein, 7-O-β-d-glucopyranoside] [Go 6976] [PD 406976] Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 5 mg 38 29 25 4,200 1 mg 117 85 73 9,600 10 mg 49 38 32 5,500 5 mg 470 342 291 38,400 25 mg 73 56 48 8,200 10 mg 920 669 571 75,200 50 mg 117 90 77 13,100 25 mg 2250 1635 1395 183,900 100 mg 164 127 108 18,300 NOTE: Euro, Pound and Yen prices are revised regularly. 250 mg 365 282 241 40,800 Please visit www.LCLabs.com for our current prices. 500 mg 660 510 436 73,800 M.W. 378.43 C24H18N4O [136194-77-9] 1 g 1175 908 777 131,400 Storage: Store at or below -20 °C. Solubility: Soluble in NOTE: Euro, Pound and Yen prices are revised regularly. DMSO at 25 mg/mL; very poorly soluble in ethanol; very Please visit www.LCLabs.com for our current prices. poorly soluble in water; maximum solubility in plain water M.W. 446.40 c H O [40246-10-4] is estimated to be about 1-5 µM; buffers, serum, or other 22 22 10 additives may increase or decrease the aqueous solubility. Storage: Store at or below -20 °C. Solubility: Soluble Appearance: Off-white to yellow solid. Disposal: A in DMSO at 200 mg/mL; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain • Novel, very potent PKC inhibitor with high selectivity for the water is estimated to be about 25-50 µM; buffers, serum, A-group of PKC isotypes (α, β and γ), with IC50 values in the 2-10 or other additives may increase or decrease the aqueous nM range. Little or no inhibition of the B- and C-groups of PKC solubility. Disposal: A isotypes, even at much higher concentrations. Kleinschroth, J., Hartenstein, J., Rudolph, C. and Schächtele, C., “Non-glycosidic/ NOTE: This highly purified glycitin is very insoluble in non-aminoalkyl-substituted indolocarbazoles as inhibitors of aqueous alcohol or aqueous acetonitrile; with heating, protein kinase C.” Bioorg. Med. Chem. Lett. 3: 1959-1964 (1993). a solution of 100 µg/mL can be made, but upon Martiny-Baron, G., Kazanietz, M.G., Mischak, H., Blumberg, P., cooling most of the glycitein crystallizes out, leaving Kochs, G., Hug, H., Marme, D. and Schächtele, C., “Selective approximately 10 µg/mL or less in solution. inhibition of protein kinase C isozymes by the indolo-carbazole • Isoflavone derivative found in soy-based food products. Wang, Gö 6976.” J. Biol. Chem. 268: 9194-9197 (1993). H. and Murphy, P.A., “Isoflavone content in commercial soybean • Please request Technical Note #2 for additional information about foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). the nomenclature of PKC isotypes. • See the extensive comments before the listing for Genistein • Sold for laboratory or manufacturing purposes only; not for (Cat. No. G-6055 on page 48). human, medical, veterinary, food, or household use. • LC Laboratories® is pleased to be the first source of glycitin at • USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese prices low enough for routine study of this important dietary soy Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent constituent. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • See also these related products: Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) - 6"-O-Acetylglycitin (Cat. No. A-7860 on page 3). Section 68B of the Patents Act of 1953 in New Zealand together - Glycitein (Cat. No. G-1152 on page 49). with the amendment of same by the Statutes Amendment Bill of - 6"-O-Malonylglycitin (Cat. No. M-4620 on page 68). 2002; (vii) such related legislation and/or case law as may be or • Sold for laboratory or manufacturing purposes only; not for become applicable in the aforementioned countries; and (viii) such human, medical, veterinary, food, or household use. similar laws and rules as may apply in various other countries.

OH H O N MeO O OH

O O O

OH N N HO Me HO

Glycitin 6''-O-Acetate — see 6"-O-Acetylglycitin CN (Cat. No. A-7860 on page 3). Gö 5549 — see CI-994, Free Base (Cat. No. C-2606 on page 21). Glycitin 6''-O-Malonate — see 6"-O-Malonylglycitin, Free Acid (Cat. No. M-4620 on page 68). Go 6976 — see Gö 6976 (Cat. No. G-6203 on page 50). Goe 5549 — see CI-994, Free Base (Cat. No. C-2606 on page 21). GP 1-110 — see AICAR, Free Base (Cat. No. A-1098 on page 5). GSK 572016 — see Lapatinib, Free Base (Cat. No. L-4899 on page 62). GSK-1120212 — see Trametinib (Cat. No. T-8123 on page 117). GSK-1363089 — see Foretinib, Free Base (Cat. No. F-4185 on page 43). GSK-3 Inhibitor XVI — see CHIR99021, Free Base (Cat. No. C-6556 on page 20). GSK-516 — see GW501516, Free Acid (Cat. No. G-4789 on page 51).

50 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

GSK089 — see Foretinib, Free Base (Cat. No. F-4185 on page 43). G-4789 GW501516, Free Acid, >99% GW 572016 — see Lapatinib, Free Base (Cat. No. L-4899 on page 62). Synonyms: [GSK-516] [GW1516] GW 572016X — see Lapatinib, Free Base Size US$ ¤ £ ¥ (Cat. No. L-4899 on page 62). 1 mg 38 28 24 4,000 GW-572016 — see Lapatinib Di-p-Toluenesulfonate Salt 5 mg 49 38 32 5,500 (Cat. No. L-4804 on page 63). 10 mg 78 60 52 8,700 GW-786034 — see Pazopanib, Free Base 25 mg 155 120 102 17,300 (Cat. No. P-6706 on page 81). 10 mg 490 379 324 54,800 300 mg 744 575 492 83,200 GW1516 — see GW501516, Free Acid (Cat. No. G-4789 on page 51). 500 mg 1120 866 740 125,200 G-5903 GW2580, Free Base, >99% NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. [cFMS Receptor Tyrosine Kinase Inhibitor] M.W. 453.50 c H F NO S [317318-70-0] [CSF-1 Receptor Inhibitor] 21 18 3 3 2 Storage: Store at or below -20 ºC. Solubility: Soluble in Size US$ ¤ £ ¥ DMSO. Disposal: A 100 mg 94 71 60 7,300 • GW501516 is a potent and selective peroxisome proliferator- 300 mg 225 170 143 17,500 activated receptor (PPAR) β/δ modulator. 1 g 485 367 308 37,700 • In vitro, GW501516 increased expression of the reverse 5 g 1875 1420 1190 145,600 cholesterol transporter ATP-binding cassette A1 and induced 10 g 2910 2204 1846 226,000 apolipoprotein A1-specific cholesterol efflux. In vivo, GW501516 NOTE: Euro, Pound and Yen prices are revised regularly. dramatically increased serum high density lipoprotein cholesterol Please visit www.LCLabs.com for our current prices. while lowering the levels of small-dense low density lipoprotein, M.W. 366.41 c H N O [870483-87-7] fasting triglycerides, and fasting insulin when dosed to insulin- 20 22 4 3 resistant middle-aged obese rhesus monkeys. Oliver, W.R., Jr. Storage: Store at or below -20 °C. Solubility: Soluble in et al., “A selective peroxisome proliferator-activated DMSO at 40 mg/mL; very poorly soluble in ethanol; very receptor δ agonist promotes reverse cholesterol transport.” poorly soluble in water; maximum solubility in plain water Proc. Natl. Acad. Sci. USA 98: 5306‑5311 (2001). is estimated to be about 20-100 µM; buffers, serum, or other additives may increase or decrease the aqueous • Treatment of skeletal muscle cells by GW501516 resulted in the solubility. Disposal: A expression of genes involved in lipid utilization, β-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, the • GW2580 is a small-molecule inhibitor of cFMS kinase; at treatment also increased apolipoprotein-A1 specific efflux 60 nM it inhibited human cFMS kinase completely in vitro of intracellular cholesterol, indicating the muscle tissue is and was inactive against 26 other kinases. GW2580 inhibited an important target of PPARβ/δ agonists. Dressel, U. et al., lipopolysaccharide (LPS)-induced TNF production in mice, “The peroxisome proliferator-activated receptor β/δ agonist, but not LPS-induced TNF production in freshly isolated human GW501516, regulates the expression of genes involved in lipid monocytes and mouse macrophages in vitro. Also, GW2580 catabolism and energy uncoupling in skeletal muscle cells.” at 1 µM totally inhibited CSF-1-induced growth of mouse Mol. Endocrinol. 17: 2477‑2493 (2003). M-NFS-60 myeloid cells and human monocytes, and prevented • GW501516 induced fatty acid β-oxidation in L6 myotubes bone degradation in cultures of rat calvaria and rat fetal long and in mouse skeletal muscles. GW501516 treatment to mice bone in vitro. Conway J.G. et al., “Inhibition of colony- fed a high-fat diet ameliorated diet-induced obesity as well stimulating-factor-1 signaling in vivo with the orally bioavailable as insulin resistance. GW501516 treatment also dramatically cFMS kinase inhibitor GW2580.” Proc. Natl. Acad. Sci. USA improved diabetes, as demonstrated by the decrease in plasma 102: 16078‑16083 (2005). glucose and blood insulin levels in genetically obese ob/ob mice. • In an arthritic rat model, GW2580 inhibited joint connective tissue Tanaka, T. et al., “Activation of peroxisome proliferator-activated and bone destruction, and thus preserved joint integrity. Conway receptor δ induces fatty acid β-oxidation in skeletal muscle and J.G. et al., “Effects of the cFMS kinase inhibitor 5-(3-methoxy- attenuates metabolic syndrome.” Proc. Natl. Acad. Sci. USA 4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine 100: 15924‑15929 (2003). (GW2580) in normal and arthritic rats.” J. Pharmacol. Exp. Ther. • GW501516 protected against cytotoxin-induced SH-SY5Y 326: 41-50 (2008). cell injury in vitro. It also significantly attenuated the ischemic • Sold for laboratory or manufacturing purposes only; not for brain damage and MPTP-induced depletion of striatal dopamine human, medical, veterinary, food, or household use. and related metabolite contents in mouse brain. Iwashita, A. • This product is offered for R&D use in accordance with (i) 35 et al., “Neuroprotective efficacy of the peroxisome proliferator- USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese activated receptor δ-selective agonists in vitro and in vivo.” Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent J. Pharmacol. Exp. Ther. 320: 1087‑1096 (2007). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • GW501516 treatment did not stimulate the growth of human Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) cancer cell lines including HT29, HCT116, LS-174T, HepG2, and other common law exemptions of Canadian patent law; (vi) and HuH7. Hollingshead, H.E. et al., “Peroxisome proliferator- Section 68B of the Patents Act of 1953 in New Zealand together activated receptor-β/δ (PPARβ/δ) ligands do not potentiate growth with the amendment of same by the Statutes Amendment Bill of of human cancer cell lines.” Carcinogenesis 28: 2641‑2649 (2007). 2002; (vii) such related legislation and/or case law as may be or • GW501516 was identified as an orally active agent that would become applicable in the aforementioned countries; and (viii) such mimic or potentiate the effects of exercise. Narkar, V.A. et al., similar laws and rules as may apply in various other countries. “AMPK and PPARδ agonists are exercise mimetics.” Cell • Not available in some countries; not available to some institutions; 134: 405‑415 (2008). not available for some uses. • GW 501516 reduced the IFNγ-induced up-regulation of TNFα and NH2 inducible NO synthase, and showed anti-inflammatory activity. Defaux, A. et al., “Effects of the PPAR-β agonist GW501516 in N an in vitro model of brain inflammation and antibody-induced demyelination.” J. Neuroinflammation 6: 15 (2009). H2N N O OMe OMe

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 51 G-5903

G-5903 2010-04-03-tdr-CD-rev.eps LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• STRUCTURE ERROR ON WIKIPEDIA'S GW501516 PAGE: As

of December 21, 2012, the structure shown on the Wikipedia page SO2NH CH2CH2NH CH2CH CH Br for GW501516 is not correct—the version shown on Wikipedia is missing a methyl group on the benzene ring carrying sulfur- and .HCl oxygen-bearing substituents. N • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. H-2330 HA-1077, Dihydrochloride Salt, >99% • This product is offered for R&D use in accordance with (i) 35 [AT-877] [Eril] USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese [1-(5-Isoquinolinesulfonyl)homopiperazine, Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Dihydrochloride Salt] Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Size US$ ¤ £ ¥ and other common law exemptions of Canadian patent law; (vi) 250 mg 38 29 25 4,200 Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 500 mg 62 48 41 6,900 2002; (vii) such related legislation and/or case law as may be or 1 g 111 86 73 12,400 become applicable in the aforementioned countries; and (viii) such 2 g 194 150 128 21,700 similar laws and rules as may apply in various other countries. 5 g 390 301 258 43,600 • Not available in some countries; not available to some institutions; 10 g 660 510 436 73,800 not available for some uses. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. CH F 3 F N M.W. 364.29 c14H17N3O2S•2HCl [103745-39-7] S CH M.I. 14: 3942 F S 3

OH Storage: Store at or below -20 °C. Solubility: Very soluble O in water, up to 200 mg/mL or more; soluble in DMSO up O to about 10 mg/mL; not soluble in ethanol; addition of an aqueous solution of this dihydrochloride salt into a buffer GX15-070 — see Obatoclax, Methanesulfonate Salt solution may significantly alter its solubility. Disposal: A (Cat. No. O-3077 on page 75). • Nomenclature. Two names have been widely used for this GX15-070MS — see Obatoclax, Methanesulfonate Salt compound, “HA-1077” and “Fasudil”, and these names have (Cat. No. O-3077 on page 75). been variously and inconsistently applied to the free base (a form that LC Labs does not sell), the monohydrochloride salt and the H-5239 H-89, Dihydrochloride Salt, >99% dihydrochloride salt forms. For many years LC Labs has sold the [N-[2-(p-Bromocinnamylamino)ethyl]-5- dihydrochloride salt under the name HA-1077, Dihydrochloride isoquinolinesulfonamide, Di-HCl Salt] Salt, as described in this listing. For historical reasons and for continuity, we have elected to continue using the HA-1077 name Size US$ ¤ £ ¥ for our dihydrochloride salt product, even though we recently 10 mg 57 40 35 5,400 introduced the monohydrochloride salt form under the name 25 mg 119 83 72 11,200 Fasudil, Monohydrochloride Salt (Cat. No. F-4660 on page 40). 100 mg 399 278 242 37,700 • The monohydrochloride salt is the form used to prepare 300 mg 975 680 591 92,000 formulations of this drug for clinical use. Note that the solubility NOTE: Euro, Pound and Yen prices are revised regularly. properties of the mono- and di-HCl salts are different. Please visit www.LCLabs.com for our current prices. • Kinase inhibitor; has antivasospastic properties:

M.W. 519.28 c20H20BrN3O2S•2HCl - Asano, T. et al., “Vasodilator actions of HA1077 in vitro [127243-85-0] and in vivo putatively mediated by the inhibition of protein kinases.” Br. J. Pharmacol. 98: 1091-1100 (1989). Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 2 mg/mL with - Sasaki, Y. and Sasaki, Y., “Inhibition of myosin light chain warming; very poorly soluble in water; maximum solubility phosphorylation in cultured smooth muscle cells by HA1077, in plain water is estimated to be about 50-100 µM; buffers, a new type of vasodilator.” Biochem. Biophys. Res. Commun. serum, or other additives may increase or decrease the 171: 1182‑1187 (1990). aqueous solubility. Disposal: A - Seto, M. et al., “Effects of HA 1077, a protein kinase inhibitor, on myosin phosphorylation and tension in smooth • Potent and selective inhibitor of PKA, with an IC50 of about 50 nM. Chijiwa, T. et al., “Inhibition of forskolin-induced neurite muscle.” Eur. J. Pharmacol. 195: 267-272 (1991). outgrowth and protein phosphorylation by a newly synthesized - Shibuya, O. et al., “The effects of an intracellular calcium selective inhibitor of cyclic AMP-dependent protein kinase, antagonist HA 1077 on delayed cerebral vasospasm in dogs.” N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide Acta Neurochir. 90: 53 (1988). (H-89), of PC12D pheochromocytoma cells.” - Shirotani, M. et al., “A new type of vasodilator, HA 1077, J. Biol. Chem. 265: 5267-5272 (1990). an isoquinoline derivative, inhibits proliferation of bovine • Also inhibits PKG and the µ isotype of PKC (at about 500 nM). vascular smooth muscle cells in culture.” J. Pharmacol. Exp. In contrast, most other PKC isotypes are much more weakly Ther. 259: 738‑744 (1991). inhibited, with IC50’s in the 32 µM range. Johannes, F.-J., Prestle, - Swärd, K. et al., “Inhibition of Rho-associated kinase J., Dieterich, S., Oberhagemann, P., Link, G. and Pfizenmaier, K., blocks agonist-induced Ca2+ sensitization of myosin “Characterization of activators and inhibitors of protein kinase phosphorylation and force in guinea-pig ileum.” J. Physiol. Cµ.” Eur. J. Biochem. 227: 303-307 (1995). 522: 33-49 (2000). • Please request Technical Note #24 for additional information. - Davies, S.P. et al., “Specificity and mechanism of action of • Sold for laboratory or manufacturing purposes only; not for some commonly used protein kinase inhibitors.” human, medical, veterinary, food, or household use. Biochem. J. 351: 95-105 (2000).

52 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Potencies for inhibition of various kinases by HA-1077: Iclusig – see its active ingredient, namely Ponatinib, Free Base (Cat. No. P-7022 on page 92). Enzyme IC50 Ki Reference Rho-associated Kinase II 1.9 µM Davies, S.P. et al. I-5577 Imatinib, Free Base, >99% Protein Kinase C-Related 4 µM Davies, S.P. et al. Synonyms: [CGP-57148B] [STI-571] Kinase 2 Related Terms: [Genfatinib] [Glamox] [Gleevec] Mitogen- and Stress- 5 µM Davies, S.P. et al. [Glivec] Activated Protein Kinase 1 Size US$ ¤ £ ¥ Mitogen Activated Protein 5 µM Davies, S.P. et al. 500 mg 38 29 24 3,200 Kinase-Activated Protein 1 g 59 45 36 4,900 Kinase 1b 2 g 106 81 66 8,900 Rho-associated Kinase 10.7 µM Swärd, K. et al. 5 g 195 148 121 16,300 Myosin Light Chain 95.2 µM Swärd, K. et al. 10 g 248 188 153 20,700 Kinase 25 g 575 437 356 48,000 NOTE: Euro, Pound and Yen prices are revised regularly. Protein Kinase C 425 µM Swärd, K. et al. Please visit www.LCLabs.com for our current prices. Cyclic AMP-Dependent 1.6 µM Asano, T. et al. M.W. 493.60 c29H31N7O [152459-95-5] Protein Kinase M.I. 14: 4902 Cyclic GMP-Dependent 1.6 µM Asano, T. et al. Storage: Store at or below -20 ºC. Solubility: Soluble in Protein Kinase DMSO at 25 mg/mL with slight warming; soluble in ethanol Myosin Light Chain 36 µM Asano, T. et al. at 5 mg/mL with slight warming; very poorly soluble in Kinase water; maximum solubility in plain water is estimated to be about 5-20 µM; buffers, serum, or other additives may • The monohydrochloride salt form of this compound, Fasudil, increase or decrease the aqueous solubility. Disposal: A Monohydrochloride Salt (Cat. No. F-4660 on page 40), is marketed • This is the free base form of imatinib; please see the other form of in Japan to treat cerebral vasospasm following surgery for this product, Imatinib, Methanesulfonate Salt (Cat. No. I-5508 on subarachnoid hemorrhage and associated cerebral ischemic page 54), for further technical information. The methanesulfonate symptoms. Zhao, J. et al., “Effect of Fasudil Hydrochloride, a salt form of imatinib is used for some or all imatinib formulation Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed for use in humans. Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid • Imatinib is the active ingredient in the drug product sold under Hemorrhage.” Neurologia Medico-Chirurgica 46: 421-428 (2006). the trade name Gleevec® and the other trade names listed above The same monohydrochloride form has been or presently is in under “Related Terms”. This drug has been approved in at least human clinical trials for treatment of acute cerebral thrombosis, one country for use in patients with gastrointestinal stromal subarachnoid hemorrhage and angina pectoris. tumors, chronic myelogenous leukemia and a number of other • Related CAS numbers: 103745-39-7 for the fasudil free base and malignancies. NOTE: THE IMATINIB, FREE BASE RESEARCH 105628-07-7 for fasudil monohydrochloride salt. COMPOUND SOLD BY LC LABORATORIES IS NOT • Sold for laboratory or manufacturing purposes only; not for GLEEVEC® NOR ANY OTHER DRUG PRODUCT SPECIFIED human, medical, veterinary, food, or household use. BY THE TRADE NAMES LISTED ABOVE UNDER “RELATED TERMS” AND IS NOT FOR HUMAN USE.

NH • NOTE: the trade names listed above under “Related Terms” are N for imatinib-containing drug products and may apply variously to formulations of one or another form of imatinib, such as the free SO 2 • 2HCl base, mesylate salt, or other forms. • This imatinib product is the free base, whose CAS number is given N above. The CAS number of the methanesulfonate salt is 220127- 57-1. Halochondrine A – see Okadaic Acid (Cat. No. O-2220 on page 76), • Sold for laboratory or manufacturing purposes only; not for Okadaic Acid, Potassium Salt (Cat. No. O-7519 on page 77), and human, medical, veterinary, food, or household use. Okadaic Acid, Sodium Salt (Cat. No. O-5857 on page 77). • This product is offered for R&D use in accordance with (i) 35 HhAntag691 – see Vismodegib, Free Base USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese (Cat. No. V-4050 on page 121). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Histone Deacetylase Inhibitor I – see Entinostat, Free Base Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) (Cat. No. E-3866 on page 34). and other common law exemptions of Canadian patent law; (vi) HKI-272 – see Neratinib (Cat. No. N-6404 on page 71). Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of HL-275 – see Alvocidib, Free Base (Cat. No. A-3465 on page 6). 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such HMR-1275 – see Alvocidib, Free Base (Cat. No. A-3465 on page 6). similar laws and rules as may apply in various other countries. 4-HPR – see Fenretinide (Cat. No. F-4077 on page 41). • Not available in some countries; not available to some institutions; 14-Hydroxydaunomycin – see Doxorubicin, Hydrochloride Salt not available for some uses. (Cat. No. D-4000 on page 33) and Doxorubicin, Free Base (Cat. No. D-4099 on page 32). 14-Hydroxydaunorubicine – see Doxorubicin, Free Base (Cat. No. D-4099 on page 32). 40-O-(2-Hydroxyethyl)-rapamycin – see Everolimus (Cat. No. E-4040 on page 40).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 53 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

N Resistant Chronic Myeloid Leukemia.” Clin. Cancer Res. 11: 4941‑4947 (2005). H N N N • Imatinib is the active ingredient in the drug sold under the trade CH ® ® 3 name Gleevec in the USA or Glivec in Europe and Australia, and the other trade names listed above under “Related Terms”. H N These drugs are currently approved in at least one country for use in patients with chronic myelogenous leukemia, gastrointestinal CH 3 O N stromal tumors and a number of other malignancies. NOTE: N THE IMATINIB, METHANESULFONATE SALT RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT GLEEVEC® NOR GLIVEC® NOR ANY OTHER DRUG Imatinib Mesylate – see Imatinib, Methanesulfonate Salt PRODUCT SPECIFIED BY THE TRADE NAMES LISTED (Cat. No. I-5508 on page 54). ABOVE UNDER “RELATED TERMS” AND IS NOT FOR I-5508 Imatinib, Methanesulfonate Salt, >99% HUMAN USE. Synonyms: [CGP-57148B] [Imatinib Mesylate] • Sold for laboratory or manufacturing purposes only; not for [STI-571] human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 Related Terms: [Genfatinib] [Gleevec] [Glivec] USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Size US$ ¤ £ ¥ Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 500 mg 38 29 24 3,200 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 1 g 59 45 36 4,900 and other common law exemptions of Canadian patent law; (vi) 2 g 106 81 66 8,900 Section 68B of the Patents Act of 1953 in New Zealand together 5 g 195 148 121 16,300 with the amendment of same by the Statutes Amendment Bill of 10 g 248 188 153 20,700 2002; (vii) such related legislation and/or case law as may be or 25 g 575 437 356 48,000 become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. • Not available in some countries; not available to some institutions; not available for some uses. M.W. 589.71 C29H31N7O •CH4SO3 [220127-57-1] N N

Storage: Store at or below -20 °C. Solubility: Soluble N NH NH N in DMSO at 100 mg/mL; very poorly soluble in ethanol; . CH O S soluble in water at 200 mg/mL; buffers, serum, or other 4 3 O N additives may increase or decrease the aqueous solubility. Disposal: A Immunomycin – see Ascomycin (Cat. No. A-1040 on page 7). • Imatinib is a member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes instead of non-specifically INCB018424 – see Ruxolitinib, Free Base inhibiting rapidly dividing cells. Imatinib is used to decrease bcr- (Cat. No. R-6600 on page 100) and Ruxolitinib, Phosphate Salt abl tyrosine kinase activity, upon which some types of tumor cells (Cat. No. R-6688 on page 101). depend for growth. Imatinib works by binding to the ATP binding INCB18424 – see Ruxolitinib, Free Base site of bcr-abl and competitively inhibiting the enzyme activity of (Cat. No. R-6600 on page 100) and Ruxolitinib, Phosphate Salt the protein. Imatinib is selective for bcr-abl, though it also inhibits (Cat. No. R-6688 on page 101). other enzymes (c-kit and PDGF-R). Deininger M. and Druker B.J., “Specific Targeted Therapy of Chronic Myelogenous Leukemia IND-71677 – see Iniparib (Cat. No. I-5432 on page 56). with Imatinib.” Pharmacol. Rev. 55: 401-423 (2003). I-1711 (-)-Indolactam V, >99% • Inhibition of the bcr-abl tyrosine kinase also stimulates its entry in to the nucleus, where it is unable to perform any of its normal Size US$ ¤ £ ¥ anti-apoptopic functions. Vigneri, P. and Wang, J.Y., “Induction of 300 µg 73 52 45 5,900 apoptosis in chronic myelogenous leukemia cells through nuclear 1 mg 166 118 102 13,400 entrapment of BCR-ABL tyrosine kinase.” Nat. Med. 7: 228‑234 (2001). 5 mg 598 423 369 48,300 NOTE: Euro, Pound and Yen prices are revised regularly. • Imatinib inhibits EOL-1 cell viability (IC50 = 0.5 nM), Please visit www.LCLabs.com for our current prices. phosphorylation of a fusion protein (IC = 30 nM), and viability 50 M.W. 301.38 c H N O [90365-57-4] of BaF3 cells expressing Rhe-PDGFRα in the absence of IL-3 17 23 3 2 SPECIAL HAZARD: Weak tumor promoter. Gloves and (IC50 = 0.17 nM). Griffin J.H. et al., “Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome.” mask should be worn when using this compound. Care Proc. Natl. Acad. Sci. USA 100: 7830-7835 (2003). must be taken to avoid contact via all routes of exposure • Inhibition of CSF-1R by imatinib is competitive with ATP, with a Storage: Store at or below -20 ºC. Solubility: Soluble in Ki value of 120 nM. Guo J. et al., “Inhibition of phosphorylation DMSO or ethanol. Disposal: A of the colony-stimulating factor-1 receptor (c-Fms) tyrosine • Moderately potent indolactam activator of protein kinase C; Kd kinase in transfected cells by ABT-869 and other tyrosine kinase for binding at the PDBu site is in the micromolar range. Weak inhibitors.” Mol. Cancer Ther. 5: 1007-1013 (2006). tumor promoter. Fujiki, H. et al., “Structure-activity studies

• The IC50 values for imatinib inhibition of KBM5 and KBM7 cell on synthetic analogues (indolactams) of the tumor promoter

growth were 0.48 and 0.24 µM, respectively, while the IC50 values teleocidin.” Gann 75: 866-870 (1984). Heikkila, J. and Akerman, for imatinib in KBM5-STI571R1.0 and KBM7-STI571R1.0 cells K.E.O., “(-)-Indolactam V activates protein kinase C and were 6.40 and 3.30 µM, respectively. The calculated resistance induces changes in muscarinic receptor functions in SH-SY5Y indexes of 13.3 for KBM5-STI571R1.0 cells and 13.8 for KBM7- human neuroblastoma cells.” Biochem. Biophys. Res. Comm. STI571R1.0 confirmed comparable degrees of imatinib resistance. 162: 1207‑1213 (1989). Golemovic M. et al., “AMN107, a Novel Aminopyrimidine • Differentiation of human embryonic stem cells to pancreatic Inhibitor of Bcr-Abl, Has In vitro Activity against Imatinib- cells. Recently, the Melton group found that (-)-ILV is capable

54 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

of inducing differentiation of human and mouse embryonic stem cells (ESCs) to pancreatic cells, identified by their expresstion I-8560 Ingenol, >99% of Pdx-1 and their further differentiation to exocrine, endocrine Size US$ ¤ £ ¥ and duct cells in response to nicotinamide and bovine FGF. Chen, S. et al., “A small molecule that directs differentiation of human 1 mg 35 26 23 3,400 ESCs into the pancreatic lineage.” Nature Chemical Biology 5 mg 162 121 104 15,600 5: 258‑265 (2009). 10 mg 249 187 161 24,000 The Melton paper also showed that phorbol 12-myristate 25 mg 445 334 287 42,800 13-acetate (PMA, Cat. No. P-1680 on page 87), the widely used 50 mg 690 517 445 66,400 standard protein kinase C (PKC) activator, produced effects 100 mg 995 746 642 95,800 essentially equivalent to those of (-)-ILV, but PMA was far more 300 mg 1890 1417 1219 181,900 potent than (-)-ILV. Also, PKC inhibitors blocked the effects of NOTE: Euro, Pound and Yen prices are revised regularly. (-)-ILV. Thus, (-)-ILV appears to be acting as an ordinary PKC Please visit www.LCLabs.com for our current prices. activator in inducing differentation of the ESCs. M.W. 348.43 c20H28O5 [30220-46-3] Since PMA is about 100-fold more potent than (-)-ILV for Storage: Store at or below -20 °C. Solubility: Soluble in differentiating ESCs and about 10-fold cheaper, PMA would be DMSO or ethanol. Disposal: A far preferable to (-)-ILV from a cost point of view, assuming the further testing does not reveal any major differences between the • Extremely weak PKC activator (Ki = 30 µM). Hasler, C.M. et al., two compounds in the ESC system. “Specific binding to protein kinase C by ingenol and its induction Moreover, PMA is the most popular choice by far of of biological responses.” Cancer Res. 52: 202-208 (1992). researchers wishing to use a standard PKC activator. Researchers • Starting material for synthesis of ingenol derivatives. use thousands of vials of PMA every year from our LC Labs™ • Sold for laboratory or manufacturing purposes only; not for division, directly and through distributors like Sigma, Biomol, human, medical, veterinary, food, or household use. Cell Signaling Technolgies, Promega, Tocris, Wako and others. In contrast, (-)-ILV is rarely used, because it does not appear to H have any significantly different properties from PMA, is much less potent, and is far more expensive. Thus, PMA has long been O H the standard PKC activator used in biological research — its biological properties are very well known, and there is a huge H existing literature on its effects in hundreds of cell types. Nonetheless, some researchers may prefer to use (-)-ILV HO OH HO OH because it and its effects were extensively highlighted and characterized in the Melton paper, in contrast to the limited experiments with PMA. I-5900 Ingenol 3-Angelate, >99% Both PMA and (-)-ILV are potent skin inflammatory agents Synonyms: [Ingenol Mebutate] [Ingenyl 3-Angelate] and skin tumor promoters in mice (but are not carcinogens, an important distinction). The same is true of (-)-7-octyl-ILV, which [3-Ingenyl Angelate] [PEP005] is a more hydrophobic analog of (-)-ILV having potency about the Related Terms: [Picato®] same as PMA. Size ¤ £ ¥ For researchers who wish to avoid using even small US$ quantities of a tumor promoter, we recommend a similar phorbol- 1 mg 63 48 42 6,000 type compound known as prostratin (Cat. No. P-4462 on page 94). 5 mg 196 151 131 18,800 Prostratin has reduced skin inflammatory activity compared to 10 mg 322 248 216 30,900 PMA and is definitely not a skin tumor promoter in mice, but it 25 mg 565 435 379 54,200 faithfully mimics the effects of PMA in a wide variety of in vitro 50 mg 884 680 592 84,900 assays. [The quantities of these compounds being used in typical 100 mg 1540 1185 1032 147,900 lab studies are so small, however, that there are probably no real

safety differences among the four — PMA, (-)-ILV, (-)-7-octyl- NOTE: Euro, Pound and Yen prices are revised regularly. ILV and prostratin]. Please visit www.LCLabs.com for our current prices.

• Please request Technical Note #3 for additional information. M.W. 430.53 c25H34O6 [75567-37-2] • Sold for laboratory or manufacturing purposes only; not for SPECIAL HAZARD: TUMOR PROMOTER. Gloves and human, medical, veterinary, food, or household use. mask should be worn when using this compound. Care must be taken to prevent contact through all routes of exposure. H N N OH Storage: Store at or below -20 ºC. Solubility: Soluble in O DMSO or ethanol. Disposal: A • Protein kinase C activator; anti-cancer drug. N • Treatment with acids or bases or heating may cause rearrangement H of the angeloyl group to the 5- or 20- positions, leading to a significant decrease in potency. • Ingenol 3-angelate, also known as ingenol mebutate, is the active ingredient in the drug product sold under the trade name Picato®. This drug is currently approved in at least one country for topical use in patients with actinic keratoses. Note: The Ingenol 3-Angelate research compound sold by LC Laboratories is not Picato® and is not for human use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 55 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

I-5432 Iniparib, 99%

O Synonyms: [BSI-201] [IND-71677] [4-Iodo-3-nitrobenzamide]

Size US$ ¤ £ ¥ O HO 50 mg 32 26 21 2,500 OH OH 100 mg 59 45 37 4,800 O 200 mg 87 66 55 7,100 250 mg 99 76 62 8,100 I-9000 Ingenol 3-Angelate 20-Acetate, >99% 500 mg 135 103 85 11,000 Synonyms: [Ingenyl 3-Angelate 20-Acetate] 1 g 174 133 110 14,200 [3-Ingenyl Angelate 20-Acetate] 2 g 316 241 199 25,800 5 g 585 447 368 47,800 Size US$ ¤ £ ¥ NOTE: Euro, Pound and Yen prices are revised regularly. 1 mg 76 55 46 8,600 Please visit www.LCLabs.com for our current prices.

New! 5 mg 225 162 135 25,600 M.W. 292.03 c7H5IN2O3 [160003-66-7] 10 mg 355 255 213 40,300 M.I. 14: 10526 25 mg 598 430 359 67,900 WARNING: Somewhat light-sensitive; avoid prolonged NOTE: Euro, Pound and Yen prices are revised regularly. exposure to ambient light. Please visit www.LCLabs.com for our current prices. M.W. 472.57 C H O [82425-35-2] Storage: Store at or below -20 ºC. Solubility: Soluble in 27 36 7 DMSO at 200 mg/mL; soluble in ethanol at 12 mg/mL with SPECIAL HAZARD: TUMOR PROMOTER. Gloves and warming; very poorly soluble in water; maximum solubility mask should be worn when using this compound. Care in plain water is estimated to be about 10-20 µM; buffers, must be taken to prevent contact through all routes of serum, or other additives may increase or decrease the exposure. aqueous solubility. Disposal: A Storage: Store at or below -20 ºC. Solubility: Soluble in • Iniparib, also known as BSI-201, is a potent inhibitor of poly DMSO or ethanol. Disposal: A (ADP-ribose) polymerase-1 (PARP1). PARP1 plays an important • Protein Kinase C activator; anti-cancer drug. role in the repair of DNA damage in cells that occurs naturally or that is induced by DNA-damaging chemotherapy. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • Iniparib had significant antitumor activity in vitro and in vivo, either alone or in combination with chemotherapy in preclinical H C H 3 studies. A randomized phase II clinical trial demonstrated CH 3 that iniparib in combination with gemcitabine and carboplatin H C 3 O H improved overall survival and clinical response in patients with metastatic triple-negative breast cancer (TNBC) when H C H 3 compared with gemcitabine and carboplatin alone. Liang, H. O and Tan, A.R., “Iniparib, a PARP1 inhibitor for the potential H C HO 3 O CH treatment of cancer, including triple-negative breast cancer.” 3 OH O IDrugs 13: 646‑656 (2010). O • Iniparib was reduced transiently to 4-iodo-3-nitrosobenzamide CH 3 by tumor cells at a very low rate, which inhibited PARP by zinc ejection and killed tumor cells. Mendeleyev, J. et al., “Potential Ingenol Mebutate – see Ingenol 3-Angelate chemotherapeutic activity of 4-iodo-3-nitrobenzamide. Metabolic (Cat. No. I-5900 on page 55). reduction to the 3-nitroso derivative and induction of cell death in Ingenyl 3-Angelate – see Ingenol 3-Angelate tumor cells in culture.” Biochem. Pharmacol. 50: 705‑714 (1995). (Cat. No. I-5900 on page 55). • Growth inhibition of E-ras 20 tumorigenic malignant cells by Ingenyl 3-Angelate 20-Acetate – see Ingenol 3-Angelate iniparib was improved 4-fold when cellular GSH content was 20-Acetate (Cat. No. I-9000 on page 56). diminished by buthionine sulfoximine (BSO), but the growth rate of CV-1 non-tumorigenic cells was not affected by the drug 3-Ingenyl Angelate – see Ingenol 3-Angelate combination. Bauer, P.I. et al., “Anti-cancer action of 4-iodo- (Cat. No. I-5900 on page 55). 3-nitrobenzamide in combination with buthionine sulfoximine: 3-Ingenyl Angelate 20-Acetate – see Ingenol 3-Angelate inactivation of poly(ADP-ribose) polymerase and tumor glycolysis 20-Acetate (Cat. No. I-9000 on page 56). and the appearance of a poly(ADP-ribose) polymerase protease.” Biochem. Pharmacol. 63: 455‑462 (2002). • Another CAS number previously assigned to iniparib, namely 937799-96-7 has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.

56 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Not available in some countries; not available to some institutions; • Antibiotic that acts as a potent and selective calcium ionophore; not available for some uses. more effective than A23187. Ionomycin binds Ca2+ in the 7.0- 9.5 pH range with the resulting complex exhibiting intense UV NO 2 absorption. Liu, C. M. et al., “Characterization of ionomycin as I a calcium ionophore.” J. Biol. Chem. 253: 5892-5894 (1978).

NH Kauffman R. F. et al., “Cation transport and specificity of 2 ionomycin. Comparison with ionophore A23187 in rat liver O mitochondria.” J. Biol. Chem. 255: 2735-2739 (1980). • Ionomycin induces apoptosis in immature B cell lines, Inlyta – see its active ingredient, namely Axitinib, Free Base for example, in Burkitt lymphoma cells, and in cultured (Cat. No. A-1107 on page 7). embryonic rat cortical neurons. More mature B cell lines do Intedanib — see Nintedanib, Free Base (Cat. No. N-9077 on page 72). not undergo apoptosis, but are arrested in the G1 phase of the cell cycle. Takei, N. et al., “Ca2+ ionophore-induced apoptosis Intedanib Esylate — see Nintedanib, Ethanesulfonate Salt on cultured embryonic rat cortical neurons.” Brain Res. 652: (Cat. No. N-9055 on page 73). 65-70 (1994). Aagaard-Tillery, K.M. et al., “Differential 4-Iodo-3-nitrobenzamide – see Iniparib (Cat. No. I-5432 on page 56). activation of a calcium-dependent endonuclease in human B lymphocytes. Role in ionomycin-induced apoptosis.” J. Immunol. I-6800 Ionomycin, Calcium Salt, >99% 155: 3297‑3307 (1995). • Sold for laboratory or manufacturing purposes only; not for Size US$ ¤ £ ¥ human, medical, veterinary, food, or household use. 5 mg 59 44 37 5,300 OH 10 mg 105 79 65 9,400 OH OH 25 mg 238 178 148 21,200 O O 100 mg 832 624 516 74,200 HO HO C NOTE: Euro, Pound and Yen prices are revised regularly. 2 Please visit www.LCLabs.com for our current prices. O

M.W. 747.07 C41H70O9•Ca [56092-82-1] Storage: Store at or below -20 °C. Solubility: Soluble in Iressa – see its active ingredient, namely Gefitinib, Free Base DMSO. Disposal: A (Cat. No. G-4408 on page 45). • Antibiotic that acts as a potent and selective calcium ionophore; I-4122 Irinotecan,I-5700 Hydrochloride 2010-26-2-tdrREV.skc Salt, Trihydrate, >99% more effective than A23187. Ionomycin binds Ca2+ in the 7.0- 9.5 pH range with the resulting complex exhibiting intense UV [Campto] [Camptosar] [Camptothecin 11] [CPT-11] absorption. Liu, C. M. et al., “Characterization of ionomycin as [DQ-2805] [Topotecin] [U-101440E] a calcium ionophore.” J. Biol. Chem. 253: 5892-5894 (1978). Kauffman R. F. et al., “Cation transport and specificity of Size US$ ¤ £ ¥ ionomycin. Comparison with ionophore A23187 in rat liver 100 mg 59 46 38 4,500 mitochondria.” J. Biol. Chem. 255: 2735-2739 (1980). 200 mg 97 76 63 7,500 • Ionomycin induces apoptosis in immature B cell lines, 250 mg 115 90 74 8,900 for example, in Burkitt lymphoma cells, and in cultured 500 mg 244 190 157 18,800 embryonic rat cortical neurons. More mature B cell lines do 1 g 429 335 277 33,100 not undergo apoptosis, but are arrested in the G1 phase of the 2 g 636 496 410 49,000 2+ cell cycle. Takei, N. et al., “Ca ionophore-induced apoptosis 5 g 875 683 565 67,400 on cultured embryonic rat cortical neurons.” Brain Res. 652: NOTE: Euro, Pound and Yen prices are revised regularly. 65-70 (1994). Aagaard-Tillery, K.M. et al., “Differential Please visit www.LCLabs.com for our current prices. activation of a calcium-dependent endonuclease in human B M.W. 677.18 C H N O •HCl•3H O lymphocytes. Role in ionomycin-induced apoptosis.” J. Immunol. 33 38 4 6 2 155: 3297‑3307 (1995). [136572-09-3] M.I. 14: 5091 • Sold for laboratory or manufacturing purposes only; not for Storage: Store at or below -20 ºC. Solubility: Soluble human, medical, veterinary, food, or household use. in DMSO at 100 mg/mL; very poorly soluble in ethanol; soluble in water at 25 mg/mL; buffers, serum, or other OH OH OH additives may increase or decrease the aqueous solubility. Ca2+ O O Disposal: A O • Irinotecan (CPT-11) is a topoisomerase I inhibitor. It is a O2C semisynthetic analog of the natural alkaloid camptothecin and has O an active metabolite SN-38 (7-Ethyl-10-hydroxycamptothecin). During the S phase of the cell cycle, camptothecins selectively bind to and stabilize topoisomerase I-DNA complexes, inhibiting I-5700 Ionomycin, Free Acid, >99% religation, causing the accumulation of topoisomerase I-mediated single-strand DNA breaks in the DNA, and producing irreversible Size US$ ¤ £ ¥ I-6800-2010-04-03-tdr-CD-rev.eps double-strand DNA breaks that lead to cell death. Garcia- 1 mg 17 13 11 1,400 Carbonero, R. and Supko, J.G., “Current perspectives on the 5 mg 79 60 49 6,600 clinical experience, pharmacology, and continued development of 10 mg 146 111 90 12,200 the camptothecins.” Clin. Cancer Res. 8: 641-661 (2002). 25 mg 298 226 184 24,900 • Both irinotecan and topotecan have activity in vivo against L1210 NOTE: Euro, Pound and Yen prices are revised regularly. and P388 leukemia, mouse colon adenocarcinomas 38 and 51, Please visit www.LCLabs.com for our current prices. Lewis lung carcinoma, mouse breast adenocarcinoma 16/C, and M.W. 709.00 C41H72O9 [56092-81-0] human tumor xenografts of B16 melanoma and HT-29 colon Warning: Toxic. adenocarcinoma. Rothenberg, M.L., “Topoisomerase I inhibitors: Review and update.” Ann. Oncol. 8: 837-855 (1997). Storage: Store at or below -20 °C. Solubility: Soluble in • In the human tumor stem cell assay, irinotecan has activity in DMSO. Disposal: A vitro against colorectal, non-small cell lung, ovarian, breast,

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 57 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

mesothelioma, pancreas, sarcoma, and cervical cancers at low drug concentrations. Shimada, Y. et al., “Activity of CPT-11 (irinotecan I-5022 Ixabepilone, Free Base, >99% hydrochloride), a topoisomerase I inhibitor, against human tumour Synonyms: [Azaepothilone B] [BMS 247550-1] colony-forming units.” Anticancer Drugs 5: 202-206 (1994). [BMS-247550] • Irinotecan is used to treat patients with colorectal cancer. Fuchs, C. Related Terms: [Ixempra] et al., “Irinotecan in the treatment of colorectal cancer.” Cancer Treat. Rev. 32: 491-503 (2006). Size US$ ¤ £ ¥ • Irinotecan is activated by hydrolysis to its active metabolite 1 mg 129 93 77 14,700 SN-38. Kaneda, N. et al., “Metabolism and pharmacokinetics of New! 5 mg 315 226 189 35,800 the camptothecin analogue CPT-11 in the mouse.” Cancer Res. 10 mg 492 354 296 55,900 50: 1715-1720 (1990). Kawato Y. et al., “Intracellular roles of 25 mg 995 715 598 113,000 SN-38, a metabolite of the camptothecin derivative CPT-11, in the 50 mg 1660 1193 997 188,600 antitumor effect of CPT-11.” Cancer Res. 51: 4187-4191 (1991). NOTE: Euro, Pound and Yen prices are revised regularly. • SN-38 is inactivated by the enzyme UGT1A1 by glucuronidation. Please visit www.LCLabs.com for our current prices. Iyer, L. et al., “Genetic predisposition to the metabolism M.W. 506.70 C H N O S [219989-84-1] of irinotecan (CPT-11). Role of uridine diphosphate 27 42 2 5 glucuronosyltransferase isoform 1A1 in the glucuronidation of its M.I. 15: 5297 active metabolite (SN-38) in human liver microsomes.” Storage: Store at or below -20 ºC. Solubility: Soluble in J. Clin. Invest. 101: 847-854 (1998). DMSO at 90 mg/mL. Disposal: A • Irinotecan is the active ingredient in the drugs sold under the trade • Ixabepilone, also known as BMS-247550, is an epothilone B names Camptosar® in the USA and Campto® in Japan. These analog and microtubule-stabilizing agent. Ixabepilone showed drugs are currently approved in at least one country for use in potent induction of tubulin polymerization, with an EC0.01 value patients with metastatic colorectal cancer. NOTE: the irinotecan of 3.5 µM, about 2-fold lower than paclitaxel (see Paclitaxel, sold by LC Laboratories is NOT Camptosar® nor Campto® and is Cat. No. P-9600 on page 80). Ixabepilone showed activity against NOT for human use. 21 paclitaxel-sensitive and paclitaxel-resistant cell lines with IC50 • Water content may vary slightly from lot to lot. Please refer to the values of 1.4 - 34.5 nM and retained its antineoplastic activity elemental analysis of each lot for the water content. against human cancers that were naturally insensitive to paclitaxel • Sold for laboratory or manufacturing purposes only; not for or that had developed resistance to paclitaxel in vivo. Lee, F.Y. human, medical, veterinary, food, or household use. et al., "BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor • This product is offered for R&D use in accordance with (i) 35 efficacy." Clin. Cancer Res. 7: 1429‑1437 (2001). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Ixabepilone demonstrated superior preclinical characteristics, Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. including high metabolic stability, low plasma protein binding Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) (79.4%) and low susceptibility to multidrug resistance protein- and other common law exemptions of Canadian patent law; (vi) mediated efflux. Lee, F.Y. et al., "Preclinical discovery Section 68B of the Patents Act of 1953 in New Zealand together of ixabepilone, a highly active antineoplastic agent." with the amendment of same by the Statutes Amendment Bill of Cancer Chemother. Pharmacol. 63: 157‑166 (2008). 2002; (vii) such related legislation and/or case law as may be or • Combined treatment with ixabepilone and capecitabine (see become applicable in the aforementioned countries; and (viii) such Capecitabine, Cat. No. C-2799 on page 17) in an international similar laws and rules as may apply in various other countries. phase 3 study demonstrated superior efficacy to capecitabine • Not available in some countries; not available to some institutions; alone in patients with metastatic breast cancer pretreated with or not available for some uses. resistant to anthracyclines and resistant to taxanes. Thomas, E.S. et al., "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment."

N J. Clin. Oncol. 25: 5210‑5217 (2007). • Ixabepilone is the active ingredient in the drug product sold under N O ® O the trade name Ixempra . This drug is currently approved in at N least one country for use in patients with aggressive metastatic O N or locally advanced breast cancer no longer responding to currently available chemotherapies. NOTE: THE IXABEPILONE . O HCl FREE BASE RESEARCH COMPOUND SOLD BY LC . 3 H O 2 LABORATORIES IS NOT IXEMPRA® AND IS NOT FOR OH O HUMAN USE. 1-(5-Isoquinolinesulfonyl)homopiperazine, Monohydrochloride • Sold for laboratory or manufacturing purposes only; not for Salt – see Fasudil, Monohydrochloride Salt human, veterinary, food, or household use. (Cat. No. F-4660 on page 40). • This product is offered for R&D use in accordance with (i) 35 1-(5-Isoquinolinesulfonyl)homopiperazine, Dihydrochloride Salt – USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese see HA-1077 (Cat. No. H-2330 on page 52). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; not available for some uses.

58 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

CH cell anti-proliferative activity.” Proc. Amer. Assoc. Cancer Res. O 3 45: Abstract #3990 (2004). Tuman, R. et al., “Discovery of a S CH 3 novel, dual mechanism anti-angiogenic and anti-proliferative agent H C 3 H C OH with oral anti-tumor activity.” Proc. Amer. Assoc. Cancer Res. N 3 CH H C 3 45: Abstract #4558 (2004). HN 3 CH 3 • JNJ-10198409 selectively inhibited neuroblastoma cell growth ® O OH O in alamarBlue assays and rapidly induced neuroblastoma cell apoptosis without affecting the growth of primary pediatric Ixempra – see its active ingredient, namely Ixabepilone, Free Base neural crest-like stem cells. It may function by inhibiting the (Cat. No. I-5022 on page 58). activity of Src family kinases. Fujitani, M. et al., “Potent and Jakafi – see its active ingredient, namely Ruxolitinib, selective cytotoxic and cytostatic activity of JNJ-10198409 against Phosphate Salt (Cat. No. R-6688 on page 101). neuroblastoma cells.” Chiba Medical J. 88E: 27‑34 (2012). • As of October 2012, it appears that Chemical Abstracts Service Jevtana – see its active ingredient, namely Cabazitaxel is erroneously using the name "JNJ-10198409" for CAS number (Cat. No. C-2581 on page 15). 627512-69-0. The structure that Chemical Abstracts Service J-4567 JNJ-10198409, Free Base, >99% shows for CAS number 627512-69-0 is actually a double- bond tautomer of JNJ-10198409, according to J. Med. Chem. Synonyms: [PDGF Receptor Tyrosine Kinase 48: 8163‑8173 (2005). This is the publication that describes Inhibitor IV] [RWJ-540973] the discovery of JNJ-10198409 and in which the CAS number 627518-40-5 is specifically assigned to the correct structure for Size US$ ¤ £ ¥ JNJ-10198409. Thus, it appears that the correct CAS number for 1 mg 19 14 12 1,700 the correct structure is 627518-40-5, as appears near the top of this New! 5 mg 78 58 49 7,100 product entry. 10 mg 142 105 90 12,900 • Another CAS number previously assigned to this product, namely 25 mg 255 189 161 23,200 872872-33-8 has been deleted by CAS and is no longer in use. 50 mg 418 311 265 38,000 • Sold for laboratory or manufacturing purposes only; not for 100 mg 692 514 438 62,900 human, veterinary, food, or household use. 300 mg 1140 847 721 103,600 • This product is offered for R&D use in accordance with (i) 35 NOTE: Euro, Pound and Yen prices are revised regularly. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Please visit www.LCLabs.com for our current prices. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent M.W. 325.34 c H FN O [627518-40-5] Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 18 16 3 2 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Storage: Store at or below -20 ºC. Solubility: Soluble in and other common law exemptions of Canadian patent law; (vi) DMSO. Disposal: A Section 68B of the Patents Act of 1953 in New Zealand together • JNJ-10198409, also known as RWJ-540973, is a potent inhibitor with the amendment of same by the Statutes Amendment Bill of of platelet-derived growth factor receptor tyrosine kinase (PDGF- 2002; (vii) such related legislation and/or case law as may be or RTK). become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. • JNJ-10198409 has anti-PDGFR-β kinase activity with an IC50 of 4.2 nM and potent antiproliferative activity in six of eight human • Not available in some countries; not available to some institutions; tumor cell lines, with IC50 values of less than 33 nM. Ho, C.Y. not available for some uses. et al., “(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl) H phenylamines: platelet-derived growth factor receptor tyrosine N N kinase inhibitors with broad antiproliferative activity against tumor O H C cells.” J. Med. Chem. 48: 8163‑8173 (2005). 3 N F H C 3 • The in vivo inhibitory effect of JNJ-10198409 on PDGF- O RTK was confirmed in tumor tissues after administering the H compound orally in a nude mouse xenograft model of human JNK Inhibitor II – see SP600125 (Cat. No. S-7979 on page 107). LoVo colon cancer. D'Andrea, M.R. et al. “Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine JTP-74057 — see Trametinib (Cat. No. T-8123 on page 117). kinase inhibitor using immunohistochemistry and quantitative image analysis.” Mol. Cancer Ther. 4: 1198‑1204 (2005). K-2151 K-252a, >99% • Multiple UDP-glucuronosyltransferase 1A enzymes are [K252a] responsible for the glucuronidation of JNJ-10198409 in human liver microsomes. Yan, Z. et al., “N-glucuronidation of the Size US$ ¤ £ ¥ platelet-derived growth factor receptor tyrosine kinase inhibitor 5 mg 74 54 46 7,200 6,7-(dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)-(3- Prices 10 mg 119 86 74 11,600 fluoro-phenyl)-amine by human UDP-glucuronosyltransferases.” Reduced! 25 mg 246 178 152 24,000 Drug Metab. Dispos. 34: 748‑755 (2006). 50 mg 414 300 256 40,300 • JNJ-10198409 demonstrated potent anti-proliferative activities 100 mg 662 480 409 64,500 against human leukemia cells K562 and SUP-B15. It induced 250 mg 1185 858 733 115,400 cell apoptosis concentration-dependently while the remaining 500 mg 1780 1289 1101 173,400 viable cells demonstrated G2/M cell cycle arrest. Using K562 NOTE: Euro, Pound and Yen prices are revised regularly. growing as a solid tumor in nude mice, JNJ-10198409 caused Please visit www.LCLabs.com for our current prices. dose-dependent inhibition of tumor growth without overt toxicity M.W. 467.47 C H N O [97161-97-2] in vivo. Mei, J. et al., “A novel PDGFR kinase, c-ABL and 27 21 3 5 c-Kit inhibitor with unique anti-proliferative activity inducing [99533-80-9] specific cell cycle dysregulation in human leukemia cells.” Storage: Store at or below -20 ºC. Solubility: Soluble in Proc. Amer. Assoc. Cancer Res. 45: Abstract #5982 (2005). DMSO at 100 mg/mL; poorly soluble in ethanol. • JNJ-10198409 has both anti-angiogenesis and tumor cell anti- Disposal: A proliferative activities. Mei, J. et al., “A novel PDGF receptor • K-252a is a kinase inhibitor that inhibits PKA (Ki = 18 nM), tyrosine kinase inhibitor with dual anti-angiogenesis and tumor PKC (Ki = 25 nM), and PKG (Ki = 20 nM). Kase, H. et al.,

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 59 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

“K-252 compounds, novel and potent inhibitors of protein H kinase C and cyclic nucleotide-dependent protein kinases.” N Biochem. Biophys. Res. Commun. 142: 436‑440 (1987). O

• Potently inhibits CaMK (Ki = 1.8 nM), competitively with ATP and noncompetitively with the substrate. Hashimoto, Y. et al., “Potent and preferential inhibition of Ca2+/calmodulin- N N dependent protein kinase II by K252a and its derivative, KT5926.” O

Biochem. Biophys. Res. Commun. 181: 423‑429 (1991). H3C H

• Potently inhibits phosphorylase kinase (IC50 = 1.7 nM), with 300- HO fold selectivity for this enzyme over protein kinase C. Elliott, L.H. CO2H et al., “K252a is a potent and selective inhibitor of phosphorylase kinase.” Biochem. Biophys. Res. Commun. 171: 148‑154 (1990). K-9609 K-252c, >99% • Potent inhibitor of the tyrosine phosphorylation of p140prototrk; [Staurosporine Aglycone] K-252a also has a direct effect on the p140prototrk tyrosine kinase. Berg, M.M. et al., “K-252a Inhibits Nerve Growth Factor- Size US$ ¤ £ ¥ K-3351-2010-04-03-tdr-CD-rev.eps induced trk Proto-oncogene Tyrosine Phosphorylation and Kinase 1 mg 47 34 29 3,900 Activity.” J. Biol. Chem. 267: 13‑16 (1992). 5 mg 194 139 119 16,000 • Potent inhibitor of pp42/44 MAP kinase in vitro and in vivo. 10 mg 335 239 206 27,600 Lloyd, E.D. and Wooten, M.W., “pp42/44MAP kinase is a 25 mg 692 495 425 57,000 component of the neurogenic pathway utilized by nerve growth NOTE: Euro, Pound and Yen prices are revised regularly. factor in PC12 cells.” J. Neurochem. 59: 1099-1109 (1992). Please visit www.LCLabs.com for our current prices. • K-252a apparently induces apoptosis by suppressing M.W. 311.34 c H N O [85753-43-1] phosphorylation of Rb, upregulating p21, and inhibiting Cdc2 and 20 13 3 Cdc25c activity. Mohri, T. et al., “K252a induces cell cycle arrest Storage: Store at or below -20 ºC. Solubility: Soluble and apoptosis by inhibiting Cdc2 and Cdc25c.” Cancer Invest. DMSO. Appearance: Off-white solid. Disposal: A 17: 391‑395 (1999). • Inhibits PKC with IC50 of 2.5 µM and PKA at about 10-fold higher • We note that one of our competitors, AG Scientific, as of February concentrations. Kleinschroth, J. et al., “Non-glycosidic/non- 11, 2014, is claiming 99.8% purity for its K252a. This claim is aminoalkyl-substituted indolocarbazoles as inhibitors of protein not credible in general chemical terms for this complex organic kinase C.” Bioorg. Med. Chem. Lett. 3: 1959-1964 (1993). compound, nor in terms of the sensitivity and reproducibility of • We are pleased to offer this product now at >99% rather than the generally utilized analytical techniques. revious 95% purity. • Sold for laboratory or manufacturing purposes only; not for H N human, medical, veterinary, food, or household use. O

NH O

N N H H N N O K252a – see K-252a (Cat. No. K-2151 on page 59). H C H 3 Kinavet — see its active ingredient, namely Masitinib, Free Base HO O (Cat. No. M-7007 on page 68). O KRN-951 — see Tivozanib, Free Base (Cat. No. T-6466 on page 113). CH 3 KRX-0401 – see Perifosine (Cat. No. P-6522 on page 85). K-3351 K-252b KT-5555 – see Lestaurtinib (Cat. No. L-6307 on page 64). (Please inquire for availability or visit www.lclabs.com) K-4651 KT5720 Size US$ ¤ £ ¥ (Please inquire for availability or visit www.lclabs.com) 1 mg 56 46 31 6,700 5 mg 195 162 107 23,400 Size US$ ¤ £ ¥ 25 mg 780 647 429 93,600 1 mg 56 46 31 6,700 100 mg 1680 1390 924 201,600 5 mg 195 162 107 23,400 NOTE: Euro, Pound and Yen prices are revised regularly. 25 mg 780 647 429 93,600 Please visit www.LCLabs.com for our current prices. 100 mg 1680 1390 924 201,600 M.W. 453.50 c26H19N3O5 [99570-78-2] NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com fo our current prices. Storage: Store (unopened) at or below 4 °C. Solubility: Soluble in DMSO and ethanol. Disposal: A H

N • Broad spectrum protein kinase inhibitor. Hashimoto, Y. et al., O Biochem. Biophys. Res. Comm. 181: 423 (1991). Yasuzawa, T., J. Antibiot. 39: 1072 (1986).

N N O H C H 3 HO CO (CH ) CH 2 2 4 3

60 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY K-4651-2009-05-23-kedRev.SKC LISTED PRODUCT In Business for 34 Years – Since 1980

is a specific inhibitor of the mammalian target of rapamycin K-6751 KT5823 (mTOR).” Biochem. J. 421: 29‑42 (2009). (Please inquire for availability or visit www.lclabs.com) • Mechanical stress is important in proliferation of venous smooth muscle cells (SMCs) in the neointima, which contributes to Size US$ ¤ £ ¥ failure of vein grafts. Mechanical cyclic stretch activates the 1 mg 56 46 31 6,700 transcription of SGK-1 (serum- and glucocorticoid-regulated 5 mg 195 162 107 23,400 kinase-1), and Ku-0063794 inhibited SGK-1 activation in response 25 mg 780 647 429 93,600 to stretch. Cheng, J. et al., “The mechanical stress-activated 100 mg 1680 1390 924 201,600 serum-, glucocorticoid-regulated kinase 1 contributes to neointima NOTE: Euro, Pound and Yen prices are revised regularly. formation in vein grafts.” Circ. Res. 107: 1265‑1274 (2010). Please visit www.LCLabs.com fo our current prices. • Ku-0063794 inhibited mTORC1 activity at 10 nM as tested by the dephosphorylation of S6 ribosomal CH 3 protein and inhibited mTORC2 at 100 nM as tested by N O the dephosphorylation of Akt in human umbilical vein endothelial cells. It also increased MAPK phosphorylation. Dormond-Meuwly, A. et al., “The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors.”

N N Biochem. Biophys. Res. Commun. 407: 714‑719 (2011). O • Ku-0063794 inhibited growth of BCR-ABL+ Ph+ B precursor H C H 3 acute lymphoblastic leukemia cells with a GI50 of 36 nM but H C O 3 had little effect on B cell proliferation at 100 nM. Janes, M.R. OCH 3 O et al., “Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor.” Nat. Med. 16: 205‑213 (2010). K-7551 KT5926 • Ku-0063794 inhibited mTORC1 and mTORC2 in U87MG glioblastoma cells with IC values of 0.1 and 0.15 µM, (Please inquire for availability or visit www.lclabs.com) 50 K-6751-2009-05-23-kedRev.SKC respectively. It also inhibited growth of T47D breast cancer Size US$ ¤ £ ¥ cells with a GI50 of 0.35 µM. Malagu, K. et al., “The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4- 1 mg 56 46 31 6,700 diamines as potent and selective inhibitors of mTOR kinase.” 5 mg 195 162 107 23,400 Bioorg. Med. Chem. Lett. 19: 5950‑5953 (2009). 25 mg 780 647 429 93,600 • Sold for laboratory or manufacturing purposes only; not for 100 mg 1680 1390 924 201,600 human, veterinary, food, or household use. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com fo our current prices. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese H Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent N O Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6)

OCH2CH2CH3 and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of N N O 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such H C H 3 similar laws and rules as may apply in various other countries. HO CO2CH3 • Not available in some countries; not available to some institutions; not available for some uses. K-9090 KU-0063794, Free Base, >99% O Synonyms: [KU-63794]

K-7551- Size2010-04-03-tdr-CD-rev.eps US$ ¤ £ ¥ N

5 mg 33 25 21 2,600 N

10 mg 59 44 38 4,600 H C 3 25 mg 133 99 85 10,300 N N N O 50 mg 188 140 120 14,600 OCH 3 100 mg 359 268 229 27,900 CH 3 200 mg 654 488 417 50,800 HO 1 g 2295 1714 1464 178,200 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com fo our current prices.

M.W. 465.54 c25H31N5O4 [938440-64-3] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 14 mg/mL with warming; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water is estimated to be about 25-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

• Ku-0063794 inhibits both mTORC1 and mTORC2, with an IC50 value of approximately 10 nM. But it does not inhibit the activity of 76 other protein kinases and seven lipid kinases at 1000-fold higher concentrations. García-Martínez, J.M. et al., “Ku-0063794

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 61 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; K-5050 KU-55933, >99% not available for some uses. Synonyms: [ATM Kinase Inhibitor] O

Size US$ ¤ £ ¥ O N S 5 mg 52 37 31 5,900 S New! 10 mg 69 50 41 7,800

25 mg 145 104 87 16,500 O 50 mg 221 159 133 25,100 100 mg 392 282 235 44,500 KU-59436 – see Olaparib (Cat. No. O-7519 on page 77). 200 mg 645 464 387 73,300 KU-63794 – see KU-0063794, Free Base NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. (Cat. No. K-9090 on page 61).

M.W. 395.49 c21H17NO3S2 [587871-26-9] KY 12420 – see Wortmannin (Cat. No. W-2990 on page 125). Storage: Store at or below -20 ºC. Solubility: Soluble Kyocristine – see its active ingredient, namely Vincristine, in DMSO at 25 mg/mL with warming; soluble in ethanol Sulfate Salt (Cat. No. V-8400 on page 122). at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be Kyprolis – see its active ingredient, namely Carfilzomib, Free Base about 50-100 µM; buffers, serum, or other additives may (Cat. No. C-3022 on page 18). increase or decrease the aqueous solubility. Disposal: A L 683590 – see Ascomycin (Cat. No. A-1040 on page 7). • KU 55933 is an inhibitor of the oncosuppressor protein ataxia telangiectasia mutated (ATM) kinase. It inhibited ATM with L86-8275 – see Alvocidib, Free Base (Cat. No. A-3465 on page 6). an IC50 of 13 nM and a Ki of 2.2 nM. KU-55933 significantly L-4899 Lapatinib, Free Base, >99% sensitized Hela cells to the cytotoxic effects of ionizing radiation and chemotherapeutic agents including etoposide (see Etoposide, [GSK 572016] [GW 572016] [GW 572016X] Cat. No. E-4488 on page 38 and Etoposide 4'-Phosphate, Free [Tykerb] [Tyverb] Acid, Cat. No. E-4444 on page 39), amsacrine, doxorubicin (see Doxorubicin, Hydrochloride Salt, Cat. No. D-4000 on page 33 and Size US$ ¤ £ ¥ Doxorubicin, Free Base, Cat. No. D-4099 32), and camptothecin. 100 mg 38 29 25 4,200 Hickson, I. et al., "Identification and characterization of a novel 200 mg 68 53 45 7,600 and specific inhibitor of the ataxia-telangiectasia mutated kinase 300 mg 93 72 61 10,400 ATM." Cancer Res. 64: 9152‑9159 (2004). 500 mg 142 110 94 15,900 • Blocking ATM/ATR (ATM- and Rad3-related) signaling with 1 g 188 145 124 21,000 KU55933 induced senescent breast, lung, and colon carcinoma 2 g 342 264 226 38,200 cells to undergo cell death via targeting p21CIP1. Crescenzi, E. 5 g 625 483 413 69,900 et al., "Ataxia telangiectasia mutated and p21CIP1 modulate cell 10 g 980 758 648 109,600 survival of drug-induced senescent tumor cells: implications for chemotherapy." Clin. Cancer Res. 14: 1877‑1887 (2008). 25 g 1860 1438 1230 207,900 NOTE: Euro, Pound and Yen prices are revised regularly. • KU-55933 blocked the phosphorylation of Akt induced by insulin Please visit www.LCLabs.com for our current prices. and insulin-like growth factor I, inhibited cancer cell proliferation M.W. 581.06 c29H26ClFN4O4S [231277-92-2] by inducing G1 cell cycle arrest, and triggered apoptosis during serum starvation in cancer cells. A combination of KU-55933 and Storage: Store at or below -20 ºC. Solubility: Soluble in rapamycin (see Rapamycin, Cat. No. R-5000 on page 96) induced DMSO at 200 mg/mL; very poorly soluble in ethanol; very apoptosis and showed better efficacy in inhibiting the growth of poorly soluble in water; maximum solubility in plain water cancer cells than each drug alone. Li, Y. and Yang, D.Q., "The is estimated to be about 1-10 µM; buffers, serum, or other ATM inhibitor KU-55933 suppresses cell proliferation and induces additives may increase or decrease the aqueous solubility. apoptosis by blocking Akt in cancer cells with overactivated Akt." Disposal: A Mol. Cancer Ther. 9: 113‑125 (2010). • This is the free base form of lapatinib; please see our product • KU-55933 suppressed the syncytial apoptosis induced either by Lapatinib, Di-p-toluenesulfonate Salt (Cat. No. L-4804 on page wild type HIV-1 or by an HIV-1 mutant lacking integrase activity. 63) for further technical information. The di-p-toluenesulfonate Perfettini, J.L. et al., "Critical involvement of the ATM-dependent salt form of lapatinib, not the free base, is used in the lapatinib DNA damage response in the apoptotic demise of HIV-1-elicited formulation for use in humans. syncytia." PLoS One 3: e2458 (2008). • Lapatinib (as the di-p-toluenesulfonate salt) is the active ingredient • KU-55933 suppressed the replication of both wild-type and in the drug sold under the trade names Tykerb® in the US and drug-resistant HIV-1. Lau, A. et al., "Suppression of HIV-1 Tyverb® in Europe. These drugs are approved in at least one infection by a small molecule inhibitor of the ATM kinase." country to treat advanced metastatic breast cancer in conjunction Nat. Cell Biol. 7: 493‑500 (2005). with the chemotherapy drug Xeloda® (generic name, capecitabine). ® • Sold for laboratory or manufacturing purposes only; not for NOTE: the lapatinib sold by LC Laboratories is NOT Tykerb nor ® human, veterinary, food, or household use. Tyverb and is NOT for human use. • This product is offered for R&D use in accordance with (i) 35 • The CAS number of Lapatinib, Free Base is given above. The USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese CAS number of the di-p-toluenesulfonate salt (Cat. No. L-4804 on Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent page 63) is 388082-77-7. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Sold for laboratory or manufacturing purposes only; not for Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) human, medical, veterinary, food, or household use. and other common law exemptions of Canadian patent law; (vi) • This product is offered for R&D use in accordance with (i) 35 Section 68B of the Patents Act of 1953 in New Zealand together USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese with the amendment of same by the Statutes Amendment Bill of Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 2002; (vii) such related legislation and/or case law as may be or Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. become applicable in the aforementioned countries; and (viii) such Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) similar laws and rules as may apply in various other countries. and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together

62 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

with the amendment of same by the Statutes Amendment Bill of • The CAS number for the free base form of lapatinib is 2002; (vii) such related legislation and/or case law as may be or 231277‑92‑2; please see our product Lapatinib, Free Base become applicable in the aforementioned countries; and (viii) such (Cat. No. L-4899 on page 62). The CAS number for lapatinib similar laws and rules as may apply in various other countries. ditosylate monohydrate is 388082-78-8. • Not available in some countries; not available to some institutions; • Sold for laboratory or manufacturing purposes only; not for not available for some uses. human, medical, veterinary, food, or household use.

N • This product is offered for R&D use in accordance with (i) 35 O O USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese S O N Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Me N Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. H N Cl Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) H and other common law exemptions of Canadian patent law; (vi) F O Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such L-4804 Lapatinib, Di-p-Toluenesulfonate Salt, >99% L-4899-2009-10-09-kedREV.SKC similar laws and rules as may apply in various other countries. Synonyms: [GW-572016] [Lapatinib Ditosylate] • Not available in some countries; not available to some institutions; Related Terms: [Tykerb] [Tyverb] not available for some uses.

N Size US$ ¤ £ ¥ O O 100 mg 38 29 25 4,200 S O N 200 mg 68 53 45 7,600 NH 300 mg 93 72 61 10,400 NH Cl 500 mg 142 110 94 15,900 .2 C H O S F 1 g 188 145 124 21,000 7 8 3 O 2 g 342 264 226 38,200 5 g 625 483 413 69,900 10 g 980 758 648 109,600 Lapatinib Ditosylate – see Lapatinib, Di-p-Toluenesulfonate Salt 25 g 1860 1438 1230 207,900 (Cat. No. L-4804 on page 63). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Lastet — see its active ingredient, namely Etoposide (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, M.W. 925.46 C29H26ClFN4O4S •2C7H8O3S Free Acid (Cat. No. E-4444 on page 39). [388082-77-7] LBH 589 – see Panobinostat, Free Base Storage: Store at or below -20 °C. Solubility: Soluble in (Cat. No. P-3703 on page 80). DMSO at 200 mg/mL; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water LCP-Siro – see Rapamycin (Cat. No. R-5000 on page 96). is estimated to be about 1-10 µM; buffers, serum, or other LCR sulfate – see Vincristine, Sulfate Salt additives may increase or decrease the aqueous solubility. (Cat. No. V-8400 on page 122). Disposal: A • Lapatinib is an epidermal growth factor receptor (EGFR) and L-6100 Leptomycin B, Free Acid, >99% HER2/neu (ErbB-2) dual tyrosine kinase inhibitor. It binds to [CI-940] [CL-1957A] [Elactocin] [LMB] [PD-114720] the intracellular phosphorylation domain to prevent receptor (Solution in Absolute Ethanol) autophosphorylation upon ligand binding. The exact site of binding has currently not been confirmed (EGFR and ErbB2 Size US$ ¤ £ ¥ have a number of intracellular phosphorylation sites). It appears to arrest the development of breast cancer in some patients 100 µg 89 66 56 8,700 with metastatic, treatment-refractory disease. Burris H.A. III 500 µg 348 257 217 33,900 “Dual Kinase Inhibition in the Treatment of Breast Cancer: 1 mg 585 431 365 57,000 Initial Experience with the EGFR/ErbB-2 Inhibitor Lapatinib.” 2 mg 1098 810 686 107,000 Oncologist 9: 10–15 (2004). 5 mg 2625 1936 1639 255,900 • Potent inhibitor of EGFR kinase (K = 3 nM), ErbB-2 kinase NOTE: Euro, Pound and Yen prices are revised regularly. i Please visit www.LCLabs.com for our current prices. (Ki = 13 nM), ErbB-4 kinase (Ki = 347 nM). Wood E.R. et al., “A Unique Structure for Epidermal Growth Factor Receptor M.W. 540.73 C33H48O6 [87081-35-4] Bound to GW572016 (Lapatinib), Relationships among Protein M.I. 14: 5444 Conformation, Inhibitor Off-Rate, and Receptor Activity in Tumor Cells.” Cancer Res. 64: 6652-6659 (2004). Storage: Store tightly sealed at or below -20 ºC. Solubility: Soluble in methanol or ethanol. Disposal: A • Lapatinib can restore tamoxifen sensitivity in ER-positive, tamoxifen-resistant breast cancer models. Chu I. et al., “The Dual • Leptomycin B (LepB) is a potent, specific inhibitor of nuclear ErbB1/ErbB2 Inhibitor, Lapatinib (GW572016), Cooperates export signal (NES)-dependent protein export from the nucleus. with Tamoxifen to Inhibit Both Cell Proliferation- and Estrogen- Fukuda. M. et al., “CRM1 is responsible for intracellular transport Dependent Gene Expression in Antiestrogen-Resistant Breast mediated by the nuclear export signal.” Cancer.” Cancer Res. 65: 18-25 (2005). Nature 390: 308-311 (1997). • Lapatinib is the active ingredient in the drug sold under the trade • The effect of LepB on the CRM1 (exportin 1) NES receptor results names Tykerb® in the US and Tyverb® in Europe. These drugs are from selective alkylation by LepB of a single cysteine residue. approved in at least one country to treat patients with advanced Kudo, N. et al., “Leptomycin B inactivates CRM1/exportin 1 by metastatic breast cancer in conjunction with the chemotherapy covalent modification at a cysteine residue in the central conserved drug Xeloda® (generic name, capecitabine). NOTE: the lapatinib region.” Proc. Natl. Acad. Sci. USA 96: 9112-9117 (1999). sold by LC Laboratories is NOT Tykerb® nor Tyverb® and is NOT • LepB inhibits the nucleo-cytoplasmic translocation of the for human use. HIV Rev protein at nanomolar concentrations. Wolff, B. et al.,

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 63 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

“Leptomycin B is an inhibitor of nuclear export: inhibition of • STABILITY TESTING: To test LepB stability in ethanol, we nucleo-cytoplasmic translocation of the human immunodeficiency tested LepB dilutions under two different temperature conditions. virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA.” One set of samples was maintained at freezer temperatures after Chem Biol. 4: 139-147 (1997). purification and dilution, and then sent in ice to an academic • LepB also exhibits potent antitumor activity in vitro and in vivo, laboratory in Texas. A second set of samples was heated in an and possesses potent antimycotic and antibiotic activity. Tunac, oven to 60 ºC for two hours, then shipped to the same Texas lab, in J.B. et al., “Novel antitumor antibiotics, CI-940 (PD 114,720) and the middle of August, without ice or refrigeration, and the samples PD 114,721. Taxonomy, fermentation and biological activity.” were assayed for inhibition of COS cell growth. No significant J. Antibiot. 38: 460-465 (1985). differences were found between the two temperature conditions. In another test, we refluxed a sample of our LepB in ethanol (b.p. • POTENCY: LepB typically exhibits IC values in the 1 nM range, 50 78.5 ºC) for an hour; at the end of this period, HPLC analysis depending on the species, cell type, and phenomenon under study. showed that decomposition products amounted to less than 1%. • Our LepB is supplied in serum bottles with teflon-lined closures • SHIPPING CONDITIONS: We ship our LepB product at ambient containing a solution in absolute ethanol (a better solvent than temperature, without ice. All the information we have indicates methanol/water; see “Solvent” below). that LepB in ethanol solution is stable for at least many weeks, and - The 100 µg size is supplied as 185 µL of a 1 mM solution probably many months, under ambient conditions. Thus, the extra (540 µg/mL) cost of ice shipments does not appear to be justified. However, for - The 500 µg size is supplied as 925 µL of a 1 mM solution maximum long-term stability, LepB solutions should be stored at (540 µg/mL) -20 ºC or colder. - The 1 mg size is supplied as 1.85 mL of a 1 mM solution • Sold for laboratory or manufacturing purposes only; not for (540 µg/mL) human, medical, veterinary, food, or household use.

- The 2 mg size is supplied as 3.7 mL of a 1 mM solution O (540 µg/mL) - The 5 mg size is supplied as 9.25 mL of a 1 mM solution O (540 µg/mL) CH CH CH CH CH CH O • Larger quantities and higher concentrations are available—please 3 3 3 3 3 3 H C request a quotation. 3 OH • SOLVENT: WARNING -- LEPTOMYCIN B IS UNSTABLE IN DMSO. DO NOT USE ANY DMSO WITH LEPTOMYCIN O OH B. Ethanol is a better solvent for LepB than methanol for at least three reasons. First, published information indicates that LepB is L-6307 Lestaurtinib, >99% more stable in ethanol (purity unchanged after 5 months at room [KT-5555] temperature: US patent 4,771,070) than in methanol/water 70/30 (freezer temperatures required for storage for more than a few Size US$ ¤ £ ¥ days: Sigma newsletter LifeScience 2: 11 (April 2001). Second, 1 mg 68 51 44 6,700 ethanol has a significantly higher boiling point than methanol, so 5 mg 158 118 101 15,600 ethanol solutions are expected to be less susceptible to changes 25 mg 355 265 228 35,000 in concentration due to solvent evaporation. Third, LepB is a 50 mg 595 445 382 58,700 relatively hydrophobic compound, and may have a tendency to stick to plastic. Being a much stronger organic solvent than 100 mg 998 746 641 98,500 methanol/water, ethanol reduces the potential loss of LepB when 300 mg 1740 1300 1117 171,700 handled in plastic. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. • DILUTING LepB SOLUTIONS: Dilutions of LepB for dose response studies should be made in an organic solvent, preferably M.W. 439.46 c26H21N3O4 [111358-88-4] ethanol, with only the final dilution being made into culture Storage: Store at or below -20 ºC. Solubility: Soluble in medium. DMSO at 100 mg/mL; soluble in ethanol at 20 mg/mL; • STABILITY WARNING: LepB in any quantity is unstable very poorly soluble in water; maximum solubility in plain when dried down into a film. Thus, under no circumstances water is estimated to be about 10 µM; buffers, serum, or should the solvent be removed from solutions of LepB, because other additives may increase or decrease the aqueous rapid decomposition and loss of recoverable material will solubility. Disposal: A result. • Lestaurtinib is a potent inhibitor of several tyrosine kinases, • We note that another supplier, Selleck Chemicals LLC, now such as FLT-3 and TrkA, that are associated with cancer growth sells leptomycin B in a dried-down, solvent-free form. From our and progression. Schmidt-Arras, D. et al., “FLT-3 receptor experience it is highly likely that the solid form will provide far tyrosine kinase as a drug target in leukemia.” Curr. Pharm. Des. less than the amounts of leptomycin B claimed on Sellecks’ vial 10: 1867‑1883 (2004). labels. The original report describing leptomycin B stated quite • Lestaurtinib inhibited tumor growth when administered at 10 mg/ clearly that leptomycin B is unstable as a solid and cannot be kg s.c. b.i.d. 5 days a week for 21-28 days in Panc-1, AsPc-1, dried down and then successfully used at its expected potency. BxPc-3, Colo 357, and MiaPaCa2 s.c. xenografts in athymic For example, we tested a sample of dried-down leptomycin B nude mice. Reductions in tumor growth volume were 50-70%. from a different vendor by treating it with methanol, an excellent Miknyoczki, S.J. et al., “The Trk tyrosine kinase inhibitor leptomycin B solvent, and then doing an HPLC assay. The CEP-701 (KT-5555) exhibits significant antitumor efficacy result was a nice, clean-looking peak that showed high purity. in preclinical xenograft models of human pancreatic ductal HOWEVER, this is very misleading – IT WAS A NICE adenocarcinoma.” Clin. Cancer Res. 5: 2205-2212 (1999). CLEAN PEAK, BUT WHEN CAREFULLY QUANTITATED, • Lestaurtinib inhibited RET and RET phosphorylation in medullary IT CONTAINED LESS THAN 40% OF THE EXPECTED thyroid carcinoma (MTC) cells. It also blocked the growth AMOUNT OF LEPTOMYCIN B. This indicates that drying of these MTC cells in culture and tumor growth in MTC cell leptomycin B down to a solid probably results in partial xenografts. Strock, C.J. et al., “CEP-701 and CEP-751 Inhibit polymerization to a highly insoluble material that cannot be Constitutively Activated RET Tyrosine Kinase Activity and redissolved. So, we predict that use of leptomycin B in dried-solid Block Medullary Thyroid Carcinoma Cell Growth.” Cancer Res. form from any source will result in large amounts of wasted time 63: 5559‑5563 (2003). and money.

64 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• FLT3 inhibition by lestaurtinib is associated with its clinical activity in AML patients harboring FLT3-activating mutations. L-5814 Linsitinib, Free Base, >99% Smith, B.D. et al., “Single-agent CEP-701, a novel FLT-3 inhibitor, Synonyms: [OSI 906AA] [OSI-906] shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia.” Size US$ ¤ £ ¥ Blood 103: 3669-3676 (2004). 5 mg 48 35 29 6,800 Prices 10 mg 57 42 35 8,100 • Lestaurtinib is a FLT3 inhibitor that is both potent (IC50 of 2 nM) and selective (no activity on the other members of the type Reduced! 25 mg 113 83 69 16,000 III RTK family at >500 nM). Levis, M. and Small, D., “Novel 50 mg 157 115 95 22,200 FLT3 tyrosine kinase inhibitors.” Expert Opin. Investig. Drugs 100 mg 234 171 142 33,100 12: 1951‑1962 (2003). 200 mg 377 276 229 53,300 • In TF-1/ITD cells, lestaurtinib potently inhibited the 300 mg 492 360 298 69,500 phosphorylation of FLT3/ITD (IC50 < 5 nM). Lestaurtinib inhibited 500 mg 740 541 449 104,600 the proliferation of TF-1/ITD cells (IC 10 nM), but showed 50 ≈ NOTE: Euro, Pound and Yen prices are revised regularly. very little effect at 10 nM on TF-1 cells. Chen, P. et al., “FLT3/ Please visit www.LCLabs.com fo our current prices. ITD Mutation Signaling Includes Suppression of SHP-1.” M.W. 421.49 c H N O [867160-71-2] J. Biol. Chem. 280: 5361-5369 (2005). 26 23 5 • Sold for laboratory or manufacturing purposes only; not for Storage: Store at or below -20 ºC. Solubility: Soluble in human, medical, veterinary, food, or household use. DMSO at 50 mg/mL; soluble in ethanol at 3 mg/mL with warming; very poorly soluble in water; maximum solubility • This product is offered for R&D use in accordance with (i) 35 in plain water is estimated to be about 2-5 µM; buffers, USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese serum, or other additives may increase or decrease the Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent aqueous solubility. Disposal: A Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • Linsitinib, also known as OSI-906, is a novel, potent small- and other common law exemptions of Canadian patent law; (vi) molecule dual insulin-like growth factor-1 receptor (IGF-1R)/ Section 68B of the Patents Act of 1953 in New Zealand together insulin receptor (IR) kinase inhibitor. with the amendment of same by the Statutes Amendment Bill of • Linsitinib inhibited IGF-1R and IR kinases with IC50 values of 2002; (vii) such related legislation and/or case law as may be or 35 nM and 75 nM, respectively. Linsitinib potently and selectively become applicable in the aforementioned countries; and (viii) such blocked autophosphorylation of both human IGF-1R and IR, similar laws and rules as may apply in various other countries. inhibited the proliferation of a variety of tumor cell lines in vitro, • Not available in some countries; not available to some institutions; and displayed robust in vivo anti-tumor efficacy in an IGF-1R- not available for some uses. driven xenograft model when administered orally. Mulvihill, M.J. et al., “Discovery of OSI-906: a selective and orally efficacious NH O dual inhibitor of the IGF-1 receptor and insulin receptor.” Future Med. Chem. 1: 1153‑1171 (2009). • Linsitinib showed superior efficacy compared with MAB391, a selective anti-IGF-1R antibody, in human tumor xenograft models N N in which both IGF-1R and IR were phosphorylated. Buck, E. O et al., “Compensatory insulin receptor (IR) activation on inhibition H C H 3 of insulin-like growth factor-1 receptor (IGF-1R): rationale HO for cotargeting IGF-1R and IR in cancer.” Mol. Cancer Ther. OH 9: 2652‑2664 (2010). • Following a single dose of linsitinib, 18FDG-PET was shown Leurocristine sulfate – see Vincristine, Sulfate Salt to serve as a rapid, noninvasive pharmacodynamic biomarker (Cat. No. V-8400 on page 122). of IGF-1R/IR inhibition. McKinley, E.T. et al., “18FDG-PET LG 1069 – see Bexarotene (Cat. No. B-2422 on page 10). predicts pharmacodynamic response to OSI-906, a dual IGF- 1R/IR inhibitor, in preclinical mouse models of lung cancer.” LGD-1069 – see Bexarotene (Cat. No. B-2422 on page 10). Clin. Cancer Res. 17: 3332‑3340 (2011). LG100069 – see Bexarotene (Cat. No. B-2422 on page 10). • IGF-1 was shown to be overexpressed in low-grade serous ovarian carcinoma (SOC) when compared with serous borderline ovarian Lilly 37231 – see Vincristine, Sulfate Salt tumors (SBOTs) and high-grade SOCs. Low-grade SOC cell lines (Cat. No. V-8400 on page 122). were more sensitive to IGF-1 stimulation and IGF-1R inhibition than were high-grade lines. Therefore, the IGF-1 pathway is a potential therapeutic target in low-grade SOC. King, E.R. et al., “The insulin-like growth factor 1 pathway is a potential therapeutic target for low-grade serous ovarian carcinoma.” Gynecol. Oncol. 123: 13‑18 (2011). • Linsitinib blocked IGF-1 signaling in LCC6 xenograft tumors in vivo. When given once a week, combined administration simultaneously of OSI-906 and doxorubicin significantly improved the anti-tumor effect of doxorubicin. Zeng, X. et al., “Enhancement of doxorubicin cytotoxicity of human cancer cells by tyrosine kinase inhibition of insulin receptor and type I IGF receptor.” Breast Cancer Res. Treat. 133: 117‑126 (2012). • Therapeutic targeting of both IR and IGF-1R by linsitinib was shown to be more effective than targeting IGF-1R alone by MAB391 in abrogating resistance to endocrine therapy in breast cancer. Fox, E.M. et al., “A kinome-wide screen identifies the insulin/IGF-1 receptor pathway as a mechanism of escape from hormone dependence in breast cancer.” Cancer Res. 71: 6773‑6784 (2011).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 65 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Epithelial-mesenchymal transition (EMT) was demonstrated to O predict hepatocellular carcinoma cell sensitivity to linsitinib, as the epithelial phenotype was strongly associated with expression

of IGF-2 and IR, and activation of IGF-1R and IR. Induction of O N EMT by TGFβ reduced sensitivity to linsitinib. Zhao, H. et al., “Epithelial-mesenchymal transition predicts sensitivity to the dual O IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines.” Mol. Cancer Ther. 11: 503‑513 (2012). • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. L-7988 LY 294002, Hydrochloride Salt, >99% • This product is offered for R&D use in accordance with (i) 35 Size US$ ¤ £ ¥ USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 50 mg 35 25 21 4,000 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. New! 100 mg 66 47 40 7,500 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 200 mg 118 85 71 13,400 and other common law exemptions of Canadian patent law; (vi) 300 mg 168 121 101 19,100 Section 68B of the Patents Act of 1953 in New Zealand together 500 mg 274 197 165 31,100 with the amendment of same by the Statutes Amendment Bill of 1 g 525 377 315 59,600 2002; (vii) such related legislation and/or case law as may be or 2 g 978 703 587 111,100 become applicable in the aforementioned countries; and (viii) such NOTE: Euro, Pound and Yen prices are revised regularly. similar laws and rules as may apply in various other countries. Please visit www.LCLabs.com for our current prices. • Not available in some countries; not available to some institutions; M.W. 343.80 c19H17NO3•HCl [934389-88-5] not available for some uses. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 20 mg/mL with warming; soluble in ethanol at 8 mg/mL with warming; very poorly soluble in water;

N maximum solubility in plain water is estimated to be about 100-150 µM; buffers, serum, or other additives may NH 2 increase or decrease the aqueous solubility. Disposal: A

N • This research compound is the hydrochloride salt form of N N LY 294002; see the free base form of this product (LY 294002, Free Base, Cat. No. L-7962 on page 66) for further technical information about both of these research compounds. • This LY 294002 product is the hydrochloride salt, whose CAS H C OH 3 number is given above. The CAS number of the LY 294002, Free Base form is 154447-36-6. Lipodox – see Doxorubicin, Hydrochloride Salt • Sold for laboratory or manufacturing purposes only; not for (Cat. No. D-4000 on page 33) and see its active ingredient, human, veterinary, food, or household use. namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). • This product is offered for R&D use in accordance with (i) 35 LMB – see Leptomycin B (Cat. No. L-6100 on page 63). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese LS-39494 – see Alvocidib, Free Base (Cat. No. A-3465 on page 6). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Luminespib – see NVP-AUY922, Free Base Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) (Cat. No. N-5300 on page 74). and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together L-7962 LY 294002, >99% with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or Size US$ ¤ £ ¥ become applicable in the aforementioned countries; and (viii) such 50 mg 35 25 21 4,700 similar laws and rules as may apply in various other countries. 100 mg 66 48 39 8,800 • Not available in some countries; not available to some institutions; 200 mg 118 85 70 15,700 not available for some uses.

300 mg 168 121 99 22,300 O 500 mg 274 197 161 36,400 .HCl 1 g 525 378 309 69,800 2 g 978 705 576 130,000 ON NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. O

M.W. 307.34 C19H17NO3 [154447-36-6] Storage: Store at or below -20 °C. Solubility: Soluble in DMSO (up to about 40 mg/mL) or ethanol. LY-188011 – see Gemcitabine, Free Base Appearance: Off-white to cream solid. Disposal: A (Cat. No. G-4199 on page 46) and Gemcitabine, • Specific inhibitor of phosphatidylinositol 3-kinase. Vlahos, C.J. Hydrochloride Salt (Cat. No. G-4177 on page 46). et al. J. Biol. Chem. 269: 5241‑5248 (1994). LY-317615 – see Enzastaurin, Free Base • Sold for laboratory or manufacturing purposes only; not for (Cat. No. E-4506 on page 34). human, medical, veterinary, food, or household use. LY231514 – see Pemetrexed, Disodium Salt, Heptahydrate (Cat. No. P-7177 on page 84).

66 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

Novel Malonyl Forms - Daidzein (Cat. No. D-2946 on page 26). of the Soybean Isoflavones - Daidzin (Cat. No. D-7878 on page 26). • Other CAS numbers previously assigned to malonyldaidzin, Only in recent years has it been recognized that large and often pre- namely 857089-52-2 and 205431-87-4, have been deleted by CAS dominant fractions of the daidzein, genistein and glycitein in unprocessed and are no longer in use. or mildly processed soybean products occur in the 6"-O-malonyl forms, not as the free glycosides or aglycones. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. Because these compounds have only recently been found in soybean OH products, their specific biological, pharmacological and nutritional proper- O O ties are essentially unknown at the present time. Given the increasing use COOH of soy products and the many beneficial nutritional properties attributed to O the isoflavone components of those products, it appears that further stud- ies of the biological role of these novel soy isoflavones are of substantial O O O scientific and medical importance. OH LC Laboratories® now offers the three malonyl isoflavones from HO HO soybeans: 6"-O­-Malonyldaidzin (Cat. No. M-6730 on page 67), 6"-O- Malonylgenistin (Cat. No. M-8090 on page 67) and 6"-O-Malonylglycitin M-8090 6"-O-Malonylgenistin, Free Acid, >98% (Cat. No. M-4620 on page 68). Synonyms: [Genistin 6''-O-Malonate]

Mallotoxin – see Rottlerin (Cat. No. R-9630 on page 99). Size US$ ¤ £ ¥ 1 mg 59 41 36 5,600 M-6730 6"-O-Malonyldaidzin, Free Acid, >98% 5 mg 185 129 112 17,500 Synonyms: [Daidzin 6''-O-Malonate] 10 mg 295 206 179 27,800 Size US$ ¤ £ ¥ 25 mg 555 387 336 52,400 NOTE: Euro, Pound and Yen prices are revised regularly. 1 mg 59 41 36 5,600 Please visit www.LCLabs.com for our current prices. 5 mg 185 129 112 17,500 M.W. 518.42 c H O [51011-05-3] 10 mg 295 206 179 27,800 24 22 13 : Store desiccated at or below -20 °C. 25 mg 555 387 336 52,400 Storage Solubility: Soluble in DMSO, methanol, ethanol, NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. or mixtures of acetonitrile/water. Disposal: A M.W. 502.42 c H O [124590-31-4] • Isoflavone derivative found in soy-based food products. Wang, 24 22 12 H. and Murphy, P.A., “Isoflavone content in commercial soybean Storage: Store desiccated at or below -20 °C. foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). Solubility: Soluble in DMSO, methanol, ethanol, or mixtures of acetonitrile/water. Disposal: A • See the extensive comments before the listing for Genistein (Cat. No. G-6055 on page 48). • Isoflavone derivative found in soy-based food products. Wang, H. • See additional comments about malonyl isoflavones above the and Murphy, P.A., “Isoflavone content in commercial soybean entry for 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). foods.” J. Agric. Food Chem. 42: 1666‑1673 (1994). • Typical purity at time of shipment is >99%; this figure may • See the extensive comments before the listing for Genistein include small amounts of monomalonyl hemiesters other than the (Cat. No. G-6055 on page 48). 6"-isomer. • Typical purity at time of shipment is >99%; this figure may • The 1 mg size (accuracy is + ca. 2-3%) consists of a film adhering include small amounts of monomalonyl hemiesters other than the to the walls of the ampule and cannot be easily subdivided by 6"-isomer. weighing. The larger sizes contain a weighable powder. • The 1 mg size (accuracy is + ca. 2-3%) consists of a film adhering • STABILITY: Very little information about the stability of this to the walls of the ampule and cannot be easily subdivided by compound is available at present. In our experience, when stored weighing. The larger sizes contain a weighable powder. in the dry state, frozen and desiccated, this compound has retained • STABILITY: Very little information about the stability of this its original purity for several years. Our manufacturing process compound is available at present. In our experience, when stored results in a highly crystalline, stable form of this product; thus, in the dry state, frozen and desiccated, this compound has retained it does not need to be shipped on ice. Our thermal stability tests its original purity for several years. Our manufacturing process show that heating our dry product at 85 oC for 10 hours causes results in a highly crystalline, stable form of this product; thus, only ca. 1% decomposition. However, we have been informed it does not need to be shipped on ice. Our thermal stability tests that aqueous or alcoholic solutions at various pH’s can undergo show that heating our dry product at 85 oC for 10 hours causes substantial decomposition less than a day after being prepared, only ca. 1% decomposition. However, we have been informed particularly when held at room temperature. We recommend that that aqueous or alcoholic solutions at various pH’s can undergo this product be stored in bulk in the dry state, very tightly sealed, substantial decomposition less than a day after being prepared, thoroughly desiccated, at the coldest available temperature. Small particularly when held at room temperature. We recommend that working quantities of solutions should be made freshly each this product be stored in bulk in the dry state, very tightly sealed, day, just prior to use, and should be discarded at the end of the thoroughly desiccated, at the coldest available temperature. Small day. Thaw containers to room temperature prior to opening, and working quantities of solutions should be made freshly each minimize exposure to air during handling to keep moisture levels day, just prior to use, and should be discarded at the end of the low. day. Thaw containers to room temperature prior to opening, and • SHIPMENT: Shipped at ambient temperature. minimize exposure to air during handling to keep moisture levels low. • See also these related products: • See additional comments about malonyl isoflavones directly above - 6"-O-Acetylgenistin (Cat. No. A-3000 on page 3). this product entry. - Genistein (Cat. No. G-6055 on page 48). • SHIPMENT: Shipped at ambient temperature. - Genistin (Cat. No. G-5200 on page 49). • See also these related products: - 6"-O-Acetyldaidzin (Cat. No. A-6900 on page 2).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 67 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Another CAS number previously assigned to malonylgenistin, CO H 2 OH namely 857089-51-1, has been deleted by CAS and is no longer in O O use. MeO • Sold for laboratory or manufacturing purposes only; not for O human, medical, veterinary, food, or household use. O O O OH O OH O OH COOH HO O HO

O O O Marqibo – see its active ingredient, namely Vincristine, Sulfate Salt (Cat. No. V-8400 on page 122). OH HO Masitinib – see Masitinib, Free Base (Cat. No. M-7007 on page 68). HO M-7007 Masitinib, Free Base, >99% M-4620 6"-O-Malonylglycitin, Free Acid, >98% Synonyms: [AB-1010] [Masitinib] Synonyms: [Glycitin 6''-O-Malonate] Related Terms: [Kinavet] [Masivet]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 1 mg 65 45 39 6,100 10 mg 37 29 24 4,100 5 mg 185 129 112 17,500 25 mg 72 56 48 8,000 10 mg 310 216 188 29,300 50 mg 112 87 74 12,500 25 mg 590 411 357 55,700 100 mg 169 131 112 18,900 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 200 mg 213 165 141 23,800 300 mg 267 206 177 29,900 M.W. 532.46 c H O [137705-39-6] 25 24 13 500 mg 410 317 271 45,800 Storage: Store desiccated at or below -20 °C. 1 g 538 416 356 60,100 Solubility: Soluble in DMSO, methanol, ethanol, 2 g 924 714 611 103,300 or mixtures of acetonitrile/water. Disposal: A 5 g 1690 1306 1117 188,900 • Isoflavone derivative found in soy-based food products. Wang, H. NOTE: Euro, Pound and Yen prices are revised regularly. and Murphy, P.A., “Isoflavone content in commercial soybean Please visit www.LCLabs.com for our current prices. foods.” J. Agric. Food Chem. 42: 1666-1673 (1994). M.W. 498.64 c28H30N6OS [790299-79-5] • See the extensive comments before the listing for Genistein Storage: Store at or below -20 ºC. Solubility: Soluble in (Cat. No. G-6055 on page 48). DMSO at 200 mg/mL; very poorly soluble in ethanol or • See additional comments about malonyl isoflavones above the water; maximum solubility in plain water is estimated to entry for 6"-O-Malonyldaidzin (Cat. No. M-6730 on page 67). be about 10-20 µM; buffers, serum, or other additives may • Typical purity at time of shipment is >99%; this figure may increase or decrease the aqueous solubility. Disposal: A include small amounts of monomalonyl hemiesters other than the • Masitinib mesylate (AB1010) is a protein tyrosine kinase inhibitor. 6"-isomer. In vitro it has greater activity and selectivity than imatinib • The 1 mg size (accuracy is + ca. 2-3%) consists of a film adhering mesylate against the wild-type c-Kit receptor and the mutated to the walls of the ampule and cannot be easily subdivided by form in the juxtamembrane region. It also inhibits the PDGF and weighing. The larger sizes contain a weighable powder. FGFR3 receptors. BUI, B.N. et al., “Preliminary efficacy and • STABILITY: Very little information about the stability of this safety results of Masitinib administered, front line in patients with compound is available at present. In our experience, when stored advanced GIST. A phase II study.” J. of Clin. Oncology 25: 10025 in the dry state, frozen and desiccated, this compound has retained (ASCO Annual Meeting Proceedings Part I 2007). its original purity for several years. Our manufacturing process • A placebo-controlled phase III clinical trial of masitinib results in a highly crystalline, stable form of this product; thus, was performed in the dogs with nonmetastatic recurrent or it does not need to be shipped on ice. Our thermal stability tests nonresectable grade II or III mast cell tumors (MCT). Masitinib show that heating our dry product at 85 oC for 10 hours causes significantly increased overall time to tumor progression (TTP) only ca. 1% decomposition. However, we have been informed compared with placebo, regardless of whether the tumors that aqueous or alcoholic solutions at various pH’s can undergo expressed mutant or wild-type KIT. Masitinib was generally well substantial decomposition less than a day after being prepared, tolerated, with the most common adverse events being mild or particularly when held at room temperature. We recommend that moderate diarrhea or vomiting. Hahn, K.A. et al., “Masitinib is this product be stored in bulk in the dry state, very tightly sealed, safe and effective for the treatment of canine mast cell tumors.” thoroughly desiccated, at the coldest available temperature. Small J. Vet. Intern. Med. 22: 1301-1309 (2008). working quantities of solutions should be made freshly each • Masitinib treatment of patients with imatinib-resistant tumors day, just prior to use, and should be discarded at the end of the was encouraging. The safety profile of masitinib at 12mg/kg/day day. Thaw containers to room temperature prior to opening, and b.i.d. was favorable and compatible with a long-term regimen minimize exposure to air during handling to keep moisture levels for the treatment of solid cancers. Soria, J.C. et al., “Phase 1 low. dose-escalation study of oral tyrosine kinase inhibitor masitinib in • SHIPMENT: Shipped at ambient temperature. advanced and/or metastatic solid cancers.” Eur. J. Cancer. • See also these related products: Jun 19 (2009) [Epub ahead of print]. - 6"-O-Acetylglycitin (Cat. No. A-7860 on page 3). • Masitinib showed an oral bioavailability of ~60% in cats. Bellamy, - Glycitein (Cat. No. G-1152 on page 49). F. et al., “Pharmacokinetics of masitinib in cats.” Vet. Res. Commun.: Jun 16 (2009) [Epub ahead of print]. - Glycitin (Cat. No. G-2822 on page 50). • Sold for laboratory or manufacturing purposes only; not for • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. human, medical, veterinary, food, or household use. • Masitinib is the active ingredient in the drug product sold under the trade name Kinavet® in the U.S, and under the trade name Masivet® in Europe. This drug is currently approved in at least

68 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

one country for use by veterinarians for treatment of recurrent • Mocetinostat selectively inhibits histone deacetylases (HDACs) (post-surgery) or nonresectable Grade II or III cutaneous mast 1-3 and 11 at submicromolar concentrations. It blocks cancer cell cell tumors in dogs that have not previously received radiotherapy proliferation in vitro and has significant antitumor activity in vivo. and/or chemotherapy except corticosteroids. THE MASITINIB, Zhou N. et al., “Discovery of N-(2-aminophenyl)-4-[(4-pyridin- FREE BASE RESEARCH COMPOUND SOLD BY LC 3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an LABORATORIES IS NOT KINAVET® NOR MASIVET® AND orally active histone deacetylase inhibitor.” J. Med. Chem. IS FOR RESEARCH USE ONLY. 51: 4072-4075 (2008). • This product is offered for R&D use in accordance with (i) 35 • Mocetinostat induces hyperacetylation of histones, causes USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese expression of the tumor suppressor protein p21(WAF1/CIP1), and Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent inhibits proliferation of human cancer cells growing in culture. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Raeppel S. et al., “SAR and biological evaluation of analogues of Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) a small molecule histone deacetylase inhibitor N-(2-aminophenyl)- and other common law exemptions of Canadian patent law; (vi) 4-((4-(pyridin-3-yl)pyrimidin-2-ylamino)methyl)benzamide Section 68B of the Patents Act of 1953 in New Zealand together (MGCD0103).” Bioorg. Med. Chem. Lett. 19: 644-649 (2009). with the amendment of same by the Statutes Amendment Bill of • Mocetinostat demonstrated antitumor activity against 2002; (vii) such related legislation and/or case law as may be or hematological and lymphoproliferative cancers. Le Tourneau C. become applicable in the aforementioned countries; and (viii) such and Siu L.L., “Promising antitumor activity with MGCD0103, a similar laws and rules as may apply in various other countries. novel isotype-selective histone deacetylase inhibitor.” • Not available in some countries; not available to some institutions; Expert Opin. Investig. Drugs 17: 1247-1254 (2008). not available for some uses. • Mocetinostat dose-dependently inhibited HDAC activity in several human cancer cell lines and in human peripheral white blood cells. N The inhibitory effect of mocetinostat lasted for at least 8 hours in N NH NH N mice and 48 hours in patients with solid tumors. Bonfils C. et al., “Evaluation of the pharmacodynamic effects of MGCD0103 from O S N preclinical models to human using a novel HDAC enzyme assay.” Clin. Cancer Res. 14: 3441-3449 (2008). Masivet — see its active ingredient, namely Masitinib, Free Base • Sold for laboratory or manufacturing purposes only; not for (Cat. No. M-7007 on page 68). human, medical, veterinary, food, or household use. McN-R-1967 – see Fenretinide (Cat. No. F-4077 on page 41). • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese MDL 107,826A – see Alvocidib, Free Base Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent (Cat. No. A-3465 on page 6). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. ME-3167 – see (R,S)-Rolipram (Cat. No. R-2020 on page 98). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) MEK1/2 Inhibitor III – see PD 325901, Free Base Section 68B of the Patents Act of 1953 in New Zealand together (Cat. No. P-9688 on page 83). with the amendment of same by the Statutes Amendment Bill of Mekinist — see its active ingredient, namely Trametinib 2002; (vii) such related legislation and/or case law as may be or (Cat. No. T‑8123 on page 117). become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. MG 0103 — see Mocetinostat, Free Base (Cat. No. M-2433 on page 69). • Not available in some countries; not available to some institutions; not available for some uses. MG-341 — see Bortezomib, Free Base (Cat. No. B-1408 on page 11). N MGCD 0103 — see Mocetinostat, Free Base (Cat. No. M-2433 on page 69). N N H NH 2 Midostaurin — see PKC412 (Cat. No. P-7600 on page 91). H N N MK-0457 — see Tozasertib, Free Base (Cat. No. T-2304 on page 116). O MK-4016 – see Fenretinide (Cat. No. F-4077 on page 41). M-2900 Motesanib, Free Base, 99% MK-8669 — Ridaforolimus (Cat. No. R-7040 on page 97). Synonyms: [AMG-706M-2433] MLN518 — see Tandutinib, Free Base (Cat. No. T-7802 on page 110). Size US$ ¤ £ ¥ M-2433 Mocetinostat, Free Base, >99% M-2433 2010-02-1210 mg HZ_RevSKC.skc36 28 24 3,400 [MG 0103] [MGCD 0103] 25 mg 75 57 50 7,100 50 mg 112 86 74 10,700 Size US$ ¤ £ ¥ 100 mg 198 151 131 18,900 10 mg 42 31 27 3,300 200 mg 367 281 243 35,000 25 mg 58 43 37 4,500 500 mg 860 657 569 82,000 50 mg 99 74 63 7,700 1 g 1590 1216 1052 151,500 100 mg 159 119 101 12,300 NOTE: Euro, Pound and Yen prices are revised regularly. 200 mg 287 214 183 22,300 Please visit www.LCLabs.com for our current prices. 500 mg 497 371 317 38,600 M.W. 373.45 C22H23N5O [453562-69-1] 1 g 869 649 554 67,500 M.I. 14: 10338 2 g 1630 1217 1040 126,600 Storage: Store at or below -20 ºC. Solubility: Soluble in NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. DMSO at 200 mg/mL; soluble in ethanol at 40 mg/mL; very poorly soluble in water; maximum solubility in plain M.W. 396.44 c23H20N6O [726169-73-9] water is estimated to be about 50-100 µM; buffers, serum, Storage: Store at or below -20 ºC. Solubility: Soluble in or other additives may increase or decrease the aqueous DMSO. Disposal: A solubility. Disposal: A

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 69 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• This motesanib research compound (also known as AMG-706) is viable tumor fraction and blood vessel density in vivo. However, the free base. Please see the other form of this product, Motesanib, motesanib did not affect the proliferation of tumor cells in vitro. Diphosphate Salt (Cat. No. M-2999 on page 70), for further Coxon, A., et al., “Broad antitumor activity in breast cancer technical information. The phosphate salt form of motesanib xenografts by motesanib, a highly selective, oral inhibitor of is used in some or all of the motesanib formulations for use in vascular endothelial growth factor, platelet-derived growth factor, humans. and Kit receptors.” Clin. Cancer Res. 15: 110‑118 (2009). • The CAS number for this motesanib free base product is given • Motesanib inhibited mutated Kit kinase autophosphorylation. above. The CAS number of the diphosphate salt is 857876-30-3. It also suppressed kinase domain mutations conferring imatinib • Another CAS number previously assigned to motesanib free base, resistance but did not inhibit the imatinib-resistant D816V namely 894356-47-9, has been deleted by CAS and is no longer in mutant. Motesanib inhibited the proliferation of Ba/F3 cells use. expressing Kit mutants. Caenepeel, S. et al., “Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.” • Sold for laboratory or manufacturing purposes only; not for J. Exp. Clin. Cancer Res. 29: 96 (2010). human, medical, veterinary, food, or household use. • Motesanib demonstrated some antitumor activity in a Phase I • This product is offered for R&D use in accordance with (i) 35 study. Rosen, L.S. et al., “Safety, pharmacokinetics, and efficacy USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese of AMG 706, an oral multikinase inhibitor, in patients with Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent advanced solid tumors.” J. Clin. Oncol. 25: 2369‑2376 (2007). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • Motesanib inhibited thyroid tumor xenograft growth, possibly and other common law exemptions of Canadian patent law; (vi) by inhibition of angiogenesis and expression of VEGFR2 Section 68B of the Patents Act of 1953 in New Zealand together and Ret on tumor cells. Coxon, A. et al., “Antitumor Activity with the amendment of same by the Statutes Amendment Bill of of Motesanib in a Medullary Thyroid Cancer Model.” 2002; (vii) such related legislation and/or case law as may be or J. Endocrinol. Invest. (Mar 21, 2011 - Epub ahead of print). become applicable in the aforementioned countries; and (viii) such • In a phase II study, 93 patients who had progressive, locally similar laws and rules as may apply in various other countries. advanced or metastatic, radioiodine-resistant differentiated • Not available in some countries; not available to some institutions; thyroid cancer were treated with motesanib diphosphate. not available for some uses. Motesanib diphosphate induced partial responses in these patients. Anticancer responses were demonstrated in 14% of patients. H C 3 CH Disease stabilization was shown in 67% of patients. Sherman, S.I. 3 NH O et al., “Motesanib diphosphate in progressive differentiated thyroid

N cancer.” N. Engl. J. Med. 359: 31‑42 (2008). N N N H • This motesanib research compound is the diphosphate salt, whose H CAS number is given above. The CAS number of the free base is 453562-69-1. M-2999 Motesanib, Diphosphate Salt, >99% • Sold for laboratory or manufacturing purposes only; not for Synonyms: [AMG-706] human, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 Size US$ ¤ £ ¥ USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 10 mg 36 28 24 3,400 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 25 mg 75 57 50 7,100 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 50 mg 112 86 74 10,700 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 100 mg 198 151 131 18,900 and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together 200 mg 367 281 243 35,000 with the amendment of same by the Statutes Amendment Bill of 500 mg 860 657 569 82,000 2002; (vii) such related legislation and/or case law as may be or 1 g 1590 1216 1052 151,500 become applicable in the aforementioned countries; and (viii) such NOTE: Euro, Pound and Yen prices are revised regularly. similar laws and rules as may apply in various other countries. Please visit www.LCLabs.com for our current prices. • Not available in some countries; not available to some institutions; M.W. 569.44 c22H23N5O•2H3PO4 not available for some uses. [857876-30-3] M.I. 14: 10338 2H3PO4 H C . 3 CH Storage: Store at or below -20 ºC. Solubility: Soluble in 3 DMSO. Disposal: A NH O N • Motesanib, also known as AMG-706, is an orally administered N N N H multikinase inhibitor that selectively targets VEGF receptors, H platelet-derived growth factor receptors, and Kit receptors with IC50 values of 2nM (VEGFR1), 3nM (VEGFR2), 6nM (VEGFR3), 84nM (PDGFR), and 8nM (Kit). It inhibits angiogenesis and MS 27-275 — see Entinostat, Free Base (Cat. No. E-3866 on page 34). tumor growth in tumor xenografts. Polverino, A. et al., “AMG MS 275 — see Entinostat, Free Base (Cat. No. E-3866 on page 34). 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit MS 275-27 — see Entinostat, Free Base receptors, potently inhibits angiogenesis and induces regression in (Cat. No. E-3866 on page 34). tumor xenografts.” Cancer Res. 66: 8715‑8721 (2006). MTA — see Pemetrexed, Disodium Salt, Heptahydrate • This research compound is the diphosphate salt form of motesanib. (Cat. No. P-7177 on page 84). We also offer the free base form; please see Motesanib, Free Base (Cat. No. M-2900 on page 69). The diphosphate salt form of motesanib is used in some or all motesanib formulations for use in humans. • Human breast cancer xenograft models were established in athymic nude mice by implanting MCF-7 (luminal), MDA- MB-231 (mesenchymal) tumor fragments, or Cal-51 (mixed/ progenitor) tumor cells. Motesanib treatment significantly inhibited the tumor growth dose-dependently and reduced

70 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

M-5602 Mubritinib, Free Base, >99% N-6404 Neratinib, Free Base, >99% [TAK-165] [HKI-272]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 10 mg 53 41 35 5,300 5 mg 49 37 32 4,700 25 mg 115 88 75 11,400 10 mg 76 57 49 7,300 50 mg 185 142 121 18,400 25 mg 99 74 64 9,500 100 mg 325 249 213 32,300 50 mg 147 110 95 14,100 200 mg 590 452 387 58,700 100 mg 238 178 153 22,900 500 mg 1270 973 834 126,300 200 mg 438 328 282 42,200 NOTE: Euro, Pound and Yen prices are revised regularly. 500 mg 672 504 433 64,700 Please visit www.LCLabs.com for our current prices. 1 g 1170 877 755 112,600 M.W. 468.47 C25H23F3N4O2 [366017-09-6] NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol M.W. 557.04 C30H29ClN6O3 [698387-09-6] at 1.7 mg/mL; very poorly soluble in water; maximum Storage: Store at or below -20 ºC. Solubility: Soluble in solubility in plain water is estimated to be about 20‑50 µM; DMSO at 2 mg/mL with warming; very poorly soluble in buffers, serum, or other additives may increase or ethanol; very poorly soluble in water; maximum solubility decrease the aqueous solubility. Disposal: A in plain water is estimated to be about 5-20 µM; buffers, • Mubritinib is a potent inhibitor of the human epidermal growth serum, or other additives may increase or decrease the factor receptor 2 (HER2) tyrosine kinase. aqueous solubility. Disposal: A • For inhibitory testing, HER2 was expressed in the following cell • Neratinib, also known as HKI-272, is considered to be a second- types: bladder (HT1376, UMUC3, T24), kidney (ACHN), and generation inhibitor of the ErbB family of receptor kinases. prostate (DU145, LNCaP, LN-REC4). IC50 values for mubritinib Sequist, L.V. et al., “Second-Generation Epidermal Growth Factor for the bladder cancer cell lines varied from 0.09 µM to greater Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung than 25 µM. All of the prostate cancer cell lines studied were Cancer.” Oncologist 12: 325‑330 (2007). sensitive (IC50 = 0.053-4.6 µM) to mubritinib, but ACHN cells • Neratinib is an irreversible inhibitor of the epidermal growth were relatively less sensitive. In the xenograft model, treatment factor receptor (EGFR) and human epidermal growth with mubritinib for 14 days significantly inhibited growth of factor receptor 2 (HER-2) tyrosine kinases by targeting a UMUC-3 (22.9%), ACHN (26.0%), and LN-REC4 (26.5%) when cysteine residue in the ATP-binding site of the receptor. compared to control. Nagasawa, J. et al., “Novel HER2 selective Rabindran, S.K. et al., “Antitumor activity of HKI-272, an orally tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and active, irreversible inhibitor of the HER-2 tyrosine kinase.” androgen-independent prostate cancer in vitro and in vivo.” Cancer Res. 64: 3958‑3965 (2004). Int. J. Urol. 13: 587-592 (2006). • Neratinib inhibits the proliferation of HER-2 overexpressing • Sold for laboratory or manufacturing purposes only; not for human breast cancer cell lines and EGFR-dependent cells in vitro. human, medical, veterinary, food, or household use. In vivo, neratinib is active against HER-2- and EGFR-dependent • This product is offered for R&D use in accordance with (i) 35 tumor xenograft models. Rabindran, S.K. et al., “Antitumor USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese activity of HKI-272, an orally active, irreversible inhibitor of the Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent HER-2 tyrosine kinase.” Cancer Res. 64: 3958‑3965 (2004). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Acquired resistance of non-small cell lung cancers to gefitinib Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) because of a T790M mutation in the EGFR kinase domain and other common law exemptions of Canadian patent law; (vi) is circumvented by neratinib. Kwak, E.L. et al., “Irreversible Section 68B of the Patents Act of 1953 in New Zealand together inhibitors of the EGF receptor may circumvent acquired resistance with the amendment of same by the Statutes Amendment Bill of to gefitinib.” Proc. Natl. Acad. Sci. USA 102: 7665‑7670 (2005). 2002; (vii) such related legislation and/or case law as may be or • Neratinib is active against HER-2-positive breast cancer in become applicable in the aforementioned countries; and (viii) such patients. Wong, K.K. et al., “HKI-272, an irreversible pan erbB similar laws and rules as may apply in various other countries. receptor tyrosine kinase inhibitor: Preliminary phase 1 results in • Not available in some countries; not available to some institutions; patients with solid tumors.” J. Clin. Oncol. 24: 3018 (2006). not available for some uses. • Another CAS number previously assigned to neratinib, namely F C 3 736156-77-7, has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. O N N N • This product is offered for R&D use in accordance with (i) 35 N USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese O Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Myocet — see Doxorubicin, Hydrochloride Salt Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) (Cat. No. D-4000 on page 33) and see its active ingredient, and other common law exemptions of Canadian patent law; (vi) namely Doxorubicin, Free Base (Cat. No. D-4099 on page 32). Section 68B of the Patents Act of 1953 in New Zealand together NCB018424 – see Ruxolitinib, Free Base with the amendment of same by the Statutes Amendment Bill of (Cat. No. R-6600 on page 100) and Ruxolitinib, Phosphate Salt 2002; (vii) such related legislation and/or case law as may be or (Cat. No. R-6688 on page 101). become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. NCB18424 – see Ruxolitinib, Free Base (Cat. No. R-6600 on page 100) and Ruxolitinib, Phosphate Salt • Not available in some countries; not available to some institutions; (Cat. No. R-6688 on page 101). not available for some uses. Neoral — see its active ingredient, namely Cyclosporin A (Cat. No. C-6000 on page 25).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 71 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

H C O N 3 and 0.20 nM, respectively. Verstovsek S. et al., “Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, H CH N against human FIP1L1-PDGFR-alpha-expressing cells.” 3 N N N Cl Leuk. Res. 30: 1499-1505 (2006). H C O H 3 • Nilotinib is a tyrosine kinase inhibitor under investigation as a

O possible treatment for chronic myelogenous leukemia (CML). In June 2006, a Phase I clinical trial found nilotinib to have relatively N favorable safety profile and to show activity in cases of CML resistant to treatment with imatinib (Gleevec®). Nexavar — see its active ingredient, namely Sorafenib, Free Base • Nilotinib is the active ingredient in the drug sold under the trade (Cat. No. S-8599 on page 105) and Sorafenib, p-Toluenesulfonate ® Salt (Cat. No. S-8502 on page 106). name Tasigna . The drug is currently approved in at least one country for use in patients with Philadelphia Chromosome-positive N-8207 Nilotinib, Free Base, >99% chronic myeloid leukemia. NOTE: the nilotinib sold by LC ® [AMN-107] [Tasigna] Laboratories is NOT Tasigna and is NOT for human use. • As of August 6, 2013, Abcam is claiming 100% purity for its Size US$ ¤ £ ¥ Nilotinib, Free Base. This claim is not credible in general chemical 100 mg 46 33 27 6,100 terms for this complex organic compound, nor in terms of the Prices 250 mg 72 52 42 9,600 sensitivity and reproducibility of generally utilized analytical Reduced! techniques. 300 mg 81 58 48 10,800 500 mg 128 92 75 17,000 • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. 1 g 207 149 122 27,500 2 g 382 275 225 50,800 • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 5 g 825 595 486 109,600 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) M.W. 529.52 c28H22F3N7O [641571-10-0] and other common law exemptions of Canadian patent law; (vi) Storage: Store at or below -20 °C. Solubility: Soluble in Section 68B of the Patents Act of 1953 in New Zealand together DMSO at 50 mg/mL; very poorly soluble in ethanol; very with the amendment of same by the Statutes Amendment Bill of poorly soluble in water; maximum solubility in plain water 2002; (vii) such related legislation and/or case law as may be or is estimated to be about 10-20 µM; buffers, serum, or become applicable in the aforementioned countries; and (viii) such other additives may increase or decrease the aqueous similar laws and rules as may apply in various other countries. solubility. Disposal: A • Not available in some countries; not available to some institutions; • Nilotinib, a novel, selective BCR-ABL inhibitor, fits into the not available for some uses. ATP-binding site of the BCR-ABL protein with higher affinity than CF 3 imatinib. In addition to being more potent than imatinib (IC50 < 30 nM) against wild-type BCR-ABL, nilotinib is also significantly O active against 32/33 imatinib-resistant BCR-ABL mutants. NH N N Weisberg E. et al., “AMN107 (nilotinib): a novel and selective N NH

inhibitor of BCR-ABL.” Br. J. Cancer 94: 1765-1769 (2006). N N • Nilotinib inhibited the proliferation of haematopoietic cells + expressing the mutations in Ph chronic myelogenous leukemia Nincaluicolflastine — see Vinblastine, Sulfate Salt (CML) and acute lymphblastic leukaemia with IC50’s of ~ 12 (Cat. No. V-7300 on page 121). nM, thus being more potent than imatinib. Nilotinib was also effective against several imatinib-resistant Bcr-Abl mutants, but Nintedanib Esylate — see Nintedanib, Ethanesulfonate Salt not T315I. Weisberg E. et al., “Characterization of AMN-107, a (Cat. No. N-9055 on page 73). selective inhibitor of native and mutant Bcr-Abl.” Cancer Cell. N-9077 Nintedanib, Free Base, >99% 7: 129‑141 (2005). Previous Names: Intedanib, Vargatef • Nilotinib and dasatinib are respectively 20-fold (IC : 15 nM 50 Synonyms: [BIBF1120] [Intedanib] versus 280 nM) and 325-fold (IC50: 0.6 nM versus 280 nM) more potent than imatinib against cells expressing wild-type Bcr-Abl. Related Terms: [Vargatef] Similar improvements are maintained for all imatinib-resistant mutants tested, with the exception of T315I. Thus, both inhibitors Size US$ ¤ £ ¥ hold promise for treating imatinib-refractory CML. O’Hare T. 5 mg 37 27 22 4,400 et al., “In vitro activity of Bcr-Abl inhibitors AMN107 and BMS- 10 mg 56 41 33 6,700 354825 against clinically relevant imatinib-resistant Abl kinase 25 mg 123 91 72 14,800 domain mutants.” Cancer Res. 65: 4500-4505 (2005). 50 mg 198 146 117 23,800 • The effects of nilotinib were compared with those of imatinib 100 mg 322 238 190 38,700 on imatinib-sensitive (KBM5 and KBM7) and imatinib-resistant 200 mg 564 417 332 67,800 CML cell lines (KBM5-STI571R1.0 and KBM7-STI571R1.0). Compared with the antiproliferative activity of imatinib, nilotinib 500 mg 998 737 588 120,000 NOTE: Euro, Pound and Yen prices are revised regularly. was 43 times more potent in KBM5 (IC50 of 11 nM versus 480 Please visit www.LCLabs.com for our current prices. nM) and 60 times more potent in KBM7 (IC of 4 nM versus 50 M.W. 539.62 c H N O [656247-17-5] 259 nM) cells. IC50’s for nilotinib and imatinib were 2.4 µM and 31 33 5 4 6.4 µM, respectively, in KBM5-STI571R1.0, and 97 nM and 2.5 Storage: Store at or below -20 ºC. Solubility: Soluble in µM, respectively, in KBM7-STI571R1.0 cells. Golemovic M. DMSO at 25 mg/mL with warming; very poorly soluble in et al., “AMN107, a Novel Aminopyrimidine Inhibitor of Bcr-Abl, ethanol; very poorly soluble in water; maximum solubility Has In vitro Activity against Imatinib-Resistant Chronic Myeloid in plain water is estimated to be about 10-20 µM; buffers, Leukemia.” Clin. Cancer Res. 11: 4941-4947 (2005). serum, or other additives may increase or decrease the • Nilotinib was as potent as imatinib in inducing apoptosis and aqueous solubility. Disposal: A inhibiting proliferation of EOL-1 cells, with IC50 values of 0.54

72 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• This product was previously called Intedanib (Cat. No. I-9077) • A reproducible hepatic perfusion index (HPI) was determined and Vargatef (Cat No. V-9077). by using quantified gadopentetate dimeglumine (Gd-DTPA) • This research compound is the free base form of nintedanib. We concentration. The HPI decreased significantly at 28 days after also offer the ethanesulfonate salt form; please see Nintedanib, treatment with nintedanib. HPI may be useful for monitoring Ethanesulfonate Salt (Cat. No. N-9055 on page 73). antiangiogenic treatment response of hepatic metastases. Miyazaki, K. et al., “Quantitative mapping of hepatic perfusion • Nintedanib is an indolinone derivative that potently inhibits index using MR imaging: a potential reproducible tool for vascular endothelial growth factor receptor (VEGFR), platelet- assessing tumour response to treatment with the antiangiogenic derived growth factor receptor (PDGFR) and fibroblast growth compound BIBF 1120, a potent triple angiokinase inhibitor.” factor receptor (FGFR) kinase activity in enzymatic assays (table Eur. Radiol. 18: 1414‑1421 (2008). 1). It blocks mitogen-activated protein kinase and Akt signaling pathways in three cell types contributing to angiogenesis, • Nintedanib is the active ingredient in the drug formulation namely endothelial cells, pericytes, and smooth muscle cells, designated by the trade name Vargatef®. This drug has been used in human clinical trials for patients with non-small cell lung, and it inhibits cell proliferation with an EC50 of 10-80 nM. Hilberg, F. et al., “BIBF 1120: triple angiokinase inhibitor colorectal, uterine, endometrial, ovarian, and cervical cancer and with sustained receptor blockade and good antitumor efficacy.” multiple myeloma. NOTE: THE NINTEDANIB, FREE BASE Cancer Res. 68: 4774‑4782 (2008). RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT VARGATEF® AND IS NOT FOR HUMAN USE. • Table 1. In vitro kinase inhibition profile of Nintedanib (adapted from Hilberg, F. et al. 2008): • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This nintedanib product is the free base form, whose CAS Kinase IC50 (nM)* number is given above. The CAS number of the Nintedanib, VEGFR-2 (mouse) 13 ± 4 Ethanesulfonate Salt form is 656247-18-6. • Another CAS number previously assigned to Nintedanib, Free VEGFR-3 13 ± 10 Base, namely 928326-83-4, has been deleted by CAS and is no longer in use. Lck 16 ± 16 • This product is offered for R&D use in accordance with (i) 35 VEGFR-2 21 ± 13 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Flt-3 26 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. VEGFR-1 34 ± 15 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) FGFR-2 37 ± 2 Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of PDGFRα 59 ± 71 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such PDGFRβ 65 ± 7 similar laws and rules as may apply in various other countries. FGFR-1 69 ± 70 • Not available in some countries; not available to some institutions; not available for some uses. FGFR-3 108 ± 41 O Src 156 ± 40 NH NH O Lyn 195 ± 12 N O N FGFR-4 610 ± 117 N O IGF1R >1,000 InsR >4,000 N-9055 Nintedanib, Ethanesulfonate Salt, >99% CDK1 >10,000 Synonyms: [BIBF1120 Esylate] [Intedanib Esylate] [Nintedanib Esylate] CDK2 >10,000 Related Terms: [Vargatef] CDK4 >10,000 Size US$ ¤ £ ¥ Other kinases (n = 26) >10,000 5 mg 37 27 22 4,400 EGFR >50,000 New! 10 mg 56 41 33 6,700 25 mg 123 91 72 14,800 HER2 >50,000 50 mg 198 146 117 23,800 100 mg 322 238 190 38,700 * Assays performed with ATP concentrations at the respective 200 mg 564 417 332 67,800 Ki. Human kinases were tested except when stated otherwise. 500 mg 998 737 588 120,000 Phosphatase PP2A and another 25 kinases were analyzed NOTE: Euro, Pound and Yen prices are revised regularly. at 10 µM with 100 µM ATP: GSK3B, ROCKII, DYRK1A, Please visit www.LCLabs.com for our current prices. PKCα, MAPK2ERK2, HGFR, MSK1, PDK1, CHK1, M.W. 649.76 C31H33N5O4•C2H6O3S MAPKAPK2, SAPK2AP38, S6K1, SGK, CK1, CK2, PKA, [656247-18-6] M.I. 15: 5031 SAPK2BP38B2, SAPK3P38G, JNK1A1, SAPK4P38D, PHK, PKBA, CSK, CDK2/CYCLINA, PRAK (data not Storage: Store at or below -20 ºC. Solubility: Soluble in shown). DMSO at 25 mg/mL with warming; soluble in ethanol at 8 mg/mL with warming; soluble in water at 25 mg/mL with • Nintedanib significantly decreased blood vessel area and inhibited warming; buffers, serum, or other additives may increase tumour growth. Zips, D. et al., “Triple angiokinase inhibition, or decrease the aqueous solubility. Disposal: A tumour hypoxia and radiation response of FaDu human squamous cell carcinomas.” Radiother. Oncol. 92: 405‑410 (2009).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 73 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• This research compound is the ethanesulfonate salt form of and HSP90β, respectively. NVP-AUY922 showed a very high nintedanib; see the free base form of this product (Nintedanib, binding affinity to HSP90β with a Kd of 1.7 nM. NVP-AUY922 Free Base, Cat. No. N-9077 on page 72) for further technical inhibited the proliferation of human tumor cells in vitro with information about both of these research compounds. GI50 values of approximately 2 to 40 nM, inducing G1-G2 arrest • This nintedanib product is the ethanesulfonate salt, whose CAS and apoptosis. Human endothelial cells were very sensitive to number is given above. The CAS number of the Nintedanib, Free NVP-AUY922 with GI50s of 2.5-3.9 nM. NVP-AUY922 also Base form is 656247-17-5. exhibited potent antitumor efficacy in human tumor xenografts including BT474 breast, A2780 ovarian, U87MG glioblastoma, • Nintedanib is the active ingredient in the drug formulation PC3 prostate, and WM266.4 melanoma. Eccles, S.A. et al., designated by the trade name Vargatef®. This drug has been “NVP-AUY922: a novel heat shock protein 90 inhibitor active used in human clinical trials for patients with non-small cell against xenograft tumor growth, angiogenesis, and metastasis.” lung, colorectal, uterine, endometrial, ovarian, and cervical Cancer Res. 68: 2850‑2860 (2008). cancer and multiple myeloma. NOTE: THE NINTEDANIB, ETHANESULFONATE SALT RESEARCH COMPOUND SOLD • NVP-AUY922 showed impressive synergistic inhibitory effect BY LC LABORATORIES IS NOT VARGATEF® AND IS NOT with histone deacetylase inhibitors, melphalan, doxorubicin, FOR HUMAN USE. NVP-LBH589 (Panobinostat), and suberoylanilide hydroxamic acid (SAHA, Vorinostat) on the growth of multiple myeloma cell • Sold for laboratory or manufacturing purposes only; not for lines and primary myeloma cells. Kaiser, M. et al., “Synergistic human, veterinary, food, or household use. action of the novel HSP90 inhibitor NVP-AUY922 with histone • This product is offered for R&D use in accordance with (i) 35 deacetylase inhibitors, melphalan, or doxorubicin in multiple USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese myeloma.” Eur. J. Haematol. 84: 337‑344 (2010). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • NVP-AUY922 potently inhibited the proliferation of human Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. breast cancer cell lines with GI values in the range of 3 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 50 to 126 nM. NVP-AUY922 induced proliferative inhibition and other common law exemptions of Canadian patent law; (vi) concordant with HSP70 upregulation and client protein Section 68B of the Patents Act of 1953 in New Zealand together depletion. Significant growth inhibition of BT-474 tumor and with the amendment of same by the Statutes Amendment Bill of good tolerability were observed in athymic mice when NVP- 2002; (vii) such related legislation and/or case law as may be or AUY922 was administered once per week. Therapeutic effects become applicable in the aforementioned countries; and (viii) such were also concurrent with changes in pharmacodynamic markers, similar laws and rules as may apply in various other countries. including HSP90-p23 dissociation, decreases in ERBB2 and • Not available in some countries; not available to some institutions; P-AKT, and increased HSP70 protein levels. Jensen, M.R. not available for some uses. et al., “NVP-AUY922: a small molecule HSP90 inhibitor with O potent antitumor activity in preclinical breast cancer models.” O H H C S N Breast Cancer Res. 10: R33 (2008). 3 OH O H H C N • Prostate-specific antigen (PSA) may serve as a sensitive biomarker 3 O N O of Hsp90 inhibition. Oikonomopoulou, K. et al., “Evaluation N of prostate-specific antigen as a novel biomarker of Hsp90 N O CH 3 inhibition.” Clin. Biochem. 42: 1705‑1712 (2009). CH 3 • 89Zr-bevacizumab PET was concordant with the antiangiogenic response and direct antitumor effects after NVP-AUY922 NKA17 — see Perifosine (Cat. No. P-6522 on page 85). treatment. It provided a noninvasive tool to monitor tumor VEGF Novaplus — see its active ingredient, namely Etoposide levels. Nagengast, W.B. et al., “89Zr-bevacizumab PET of early (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, antiangiogenic tumor response to treatment with HSP90 inhibitor Free Acid (Cat. No. E-4444 on page 39). NVP-AUY922.” J. Nucl. Med. 51: 761‑767 (2010). • NVP-AUY922 effectively reduces human epidermal growth Novopharm – see its active ingredient, namely Vincristine, factor receptor-2 (HER2), which can be monitored with 89Zr- Sulfate Salt (Cat. No. V-8400 on page 122). trastuzumab PET in vivo non-invasively. It might serve as NPH007098 – see Delanzomib, Free Base an early biomarker for HSP90 inhibition in HER2 positive (Cat. No. D-4011 on page 28). metastatic breast cancer patients. Oude Munnink, T.H. et al., “89Zr-trastuzumab PET visualises HER2 downregulation by the N-5300 NVP-AUY922, Free Base, >99% HSP90 inhibitor NVP-AUY922 in a human tumour xenograft.” Synonyms: [AUY922] [Luminespib] [VER-52296] Eur. J. Cancer 46: 678‑684 (2010). • Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 enhanced Size US$ ¤ £ ¥ radiosensitivity in four tumor cell lines tested (A549, GaMG, 5 mg 55 40 33 6,300 HT 1080, and SNB19). Stingl, L. et al., “Novel HSP90 inhibitors, 10 mg 71 52 42 8,200 NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells 25 mg 152 111 90 17,500 through cell-cycle impairment, increased DNA damage and repair 50 mg 244 178 145 28,100 protraction.” Br. J. Cancer 102: 1578‑1591 (2010). 100 mg 345 252 205 39,800 • Sold for laboratory or manufacturing purposes only; not for 200 mg 484 353 288 55,800 human, veterinary, food, or household use. 500 mg 1145 836 681 132,000 • This product is offered for R&D use in accordance with (i) 35 NOTE: Euro, Pound and Yen prices are revised regularly. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Please visit www.LCLabs.com for our current prices. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent M.W. 465.54 c H N O [747412-49-3] Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 26 31 3 5 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Storage: Store at or below -20 ºC. Solubility: Soluble in and other common law exemptions of Canadian patent law; (vi) DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; Section 68B of the Patents Act of 1953 in New Zealand together very poorly soluble in water; maximum solubility in plain with the amendment of same by the Statutes Amendment Bill of water is estimated to be about 25-50 µM; buffers, serum, 2002; (vii) such related legislation and/or case law as may be or or other additives may increase or decrease the aqueous become applicable in the aforementioned countries; and (viii) such solubility. Disposal: A similar laws and rules as may apply in various other countries.

• NVP-AUY922 potently inhibited HSP90 with IC50 values of • Not available in some countries; not available to some institutions; 7.8 nM and 21 nM, and Ki values of 9 nM and 8.2 nM for HSP90α not available for some uses.

74 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

CH • NVP-BEZ235 inhibits the PI3K/mTOR pathway and results in 3 OH inhibition of proliferation of cancer cells with both wild-type and H C 3 mutated p110α. Serra, V. et al., “NVP-BEZ235, a dual PI3K/ N mTOR inhibitor, prevents PI3K signaling and inhibits the growth O of cancer cells with activating PI3K mutations.” Cancer Res. OH 68: 8022‑8030 (2008). O • Sold for laboratory or manufacturing purposes only; not for O N human, medical, veterinary, food, or household use. N H • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese CH 3 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. N-4288 NVP-BEZ235, Free Base, >99% Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Related Term: [BEZ235] and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together New Generic Name: [Dactolisib] with the amendment of same by the Statutes Amendment Bill of Size US$ ¤ £ ¥ 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such 25 mg 33 26 22 3,700 similar laws and rules as may apply in various other countries. 50 mg 48 37 32 5,400 • Not available in some countries; not available to some institutions; 100 mg 89 69 59 10,000 not available for some uses. 200 mg 142 110 94 15,900 250 mg 168 130 111 18,800

500 mg 285 220 188 31,900 CN

1 g 368 284 243 41,100 O N 2 g 680 526 450 76,000 N 5 g 1590 1229 1051 177,800 N NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. N M.W. 469.54 c30H23N5O [915019-65-7] Storage: Store at or below -20 ºC. Solubility: Soluble in NVP-LBH-589 — see Panobinostat, Free Base anhydrous dimethylformamide at 10 mg/mL after warming (Cat. No. P-3703 on page 80). to 75 °C and cooling; soluble in DMSO at 1.33 mg/mL Obatoclax mesylate — see Obatoclax, Methanesulfonate Salt with warming; soluble in 1-methyl-2-pyrrolidinone at (Cat. No. O-3077 on page 75). about 2 mg/mL after warming to 75 °C and cooling; very poorly soluble in ethanol; very poorly soluble in water; O-3077 Obatoclax, Methanesulfonate Salt, >99% maximum solubility in plain water is estimated to be about 10‑20 µM; buffers, serum, or other additives may increase Synonyms: [GX15-070] [GX15-070MS] or decrease the aqueous solubility. Disposal: A [Obatoclax mesylate] • NVP-BEZ235 is an imidazo[4,5-c]quinoline derivative that Size US$ ¤ £ ¥ inhibits PI3K and mTOR kinase activity by binding to the ATP- 5 mg 49 38 33 4,600 binding cleft of these enzymes. NVP-BEZ235 is able to effectively 10 mg 68 52 45 6,400 and specifically block the dysfunctional activation of the PI3K pathway and induce G(1) arrest. It also inhibits the growth of 25 mg 139 107 92 13,000 human cancer in animal models. Maira, S.M. et al., “Identification 50 mg 215 165 143 20,100 and characterization of NVP-BEZ235, a new orally available dual 100 mg 368 282 245 34,400 phosphatidylinositol 3-kinase/mammalian target of rapamycin 200 mg 559 429 372 52,300 inhibitor with potent in vivo antitumor activity.” Mol. Cancer Ther. 500 mg 896 688 596 83,900 7: 1851-1863 (2008). 1 g 1695 1301 1127 158,600 • NVP-BEZ235 strongly inhibits VEGF-induced cell proliferation NOTE: Euro, Pound and Yen prices are revised regularly. and survival in vitro and VEGF-induced angiogenesis in vivo. Please visit www.LCLabs.com for our current prices. Schnell, C.R. et al., “Effects of the Dual Phosphatidylinositol M.W. 413.49 c20H19N3O•CH4SO3 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP- [803712-79-0] BEZ235 on the Tumor Vasculature: Implications for Clinical Imaging.” Cancer Res. 68: 6598-6607 (2008). Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 5 mg/mL; very poorly soluble in ethanol; very • NVP-BEZ235 abrogated phosphatidylinositol 3-kinase poorly soluble in water; maximum solubility in plain water (PI3K)-induced lapatinib resistance. Eichhorn, P.J. et al., is estimated to be about 200-400 µM; buffers, serum, or “Phosphatidylinositol 3-Kinase Hyperactivation Results other additives may increase or decrease the aqueous in Lapatinib Resistance that Is Reversed by the mTOR/ solubility. Disposal: A Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235.” Cancer Res. 68: 9221-9230 (2008). • Obatoclax, also known as GX15-070, is a novel Bcl-2 • NVP-BEZ235 induced melanoma cells to arrest in the G1 phase homology domain-3 (BH3) mimetic. It occupies a hydrophobic of cell cycle, reduced cyclin D1 expression, and increased cleft within the BH3 binding groove of Bcl-2, antagonizing p27(KIP1), but had negligible apoptotic activity. In a syngeneic Bcl-2 and thus inducing apoptosis. Chonghaile, T.N. and B16 mouse melanoma tumor model, NVP-BEZ235 significantly Letai, A., “Mimicking the BH3 domain to kill cancer cells.” attenuated tumor growth at primary and lymph node metastatic Oncogene 27: S149‑S157 (2008). sites without obvious toxicity. In addition, NVP-BEZ235 blocked • Obatoclax inhibited primary acute myeloid leukemia neovascularization and increased tumoral necrosis. Marone, R., (AML) progenitor cell proliferation with an average IC50 of et al., “Targeting melanoma with dual phosphoinositide 3-kinase/ 0.18 ± 0.07 µM. Obatoclax potently induced apoptosis in primary mammalian target of rapamycin inhibitors.” Mol. Cancer Res. AML cells with an average IC50 of 3.6 ± 1.2 µM. Konopleva, M. 7: 601-613 (2009). et al., “Mechanisms of antileukemic activity of the novel

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 75 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Bcl-2 homology domain-3 mimetic GX15-070 (Obatoclax).” Cancer Res. 68: 3413‑3420 (2008). O-1666 ODQ, Free Base, >99% • Obatoclax had a synergistic antitumor effect with the novel Synonyms: [1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1- BH3 mimetic ABT-737 on inducing apoptosis in OCI-AML3 one] cells. It also had a synergistic antitumor effect with AraC (1-β-D-arabinofuranosyl cytosine) on inducing apoptosis in Size US$ ¤ £ ¥ leukemic cell lines and primary AML samples. Konopleva, M. 10 mg 38 27 24 2,900 et al., “Mechanisms of antileukemic activity of the novel 50 mg 85 61 53 6,500 Bcl-2 homology domain-3 mimetic GX15-070 (Obatoclax).” 100 mg 155 112 97 11,800 Cancer Res. 68: 3413‑3420 (2008). 300 mg 273 196 171 20,800 • Obatoclax overcomes Bcl-2-, Bcl-xL-, Bcl-w-, and Mcl- 1 g 670 482 420 51,100 1-mediated resistance to BAX or BAK. Obatoclax also NOTE: Euro, Pound and Yen prices are revised regularly. overcomes the Mcl-1-confered resistance to the BCL-2/ Please visit www.LCLabs.com for our current prices. BCL-XL/BCL-w-selective antagonist ABT-737 and to M.W. 187.15 C H N O [41443-28-1] the proteasome inhibitor bortezomib. Nguyen, M. et al., 9 5 3 2 “Small molecule obatoclax (GX15-070) antagonizes MCL- Storage: Store at or below -20 ºC. Solubility: Soluble in 1 and overcomes MCL-1-mediated resistance to apoptosis.” DMSO at 50 mg/mL; soluble in ethanol at 2 mg/mL with Proc. Natl. Acad. Sci. USA 104: 19512‑19517 (2007). warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 µM; buffers, • Obatoclax released Bak from Mcl-1 and Bcl-xL and induced serum, or other additives may increase or decrease the apoptosis in mantle cell lymphoma (MCL) cell lines and aqueous solubility. Disposal: A primary cells from patients with MCL. Obatoclax neutralized bortezomib-induced Mcl-1 accumulation and cooperated • ODQ is a specific inhibitor for soluble guanylyl cyclase (sGC) and with Noxa to induce Bak displacement from this protein, and is an important pharmacological tool for differentiating cGMP- synergized with bortezomib and sensitized MCL cells to low mediated from cGMP-independent effects, such as those caused by doses of this proteasome inhibitor. Pérez-Galán, P. et al., “The nitric oxide. BH3-mimetic GX15-070 synergizes with bortezomib in mantle • ODQ inhibited relaxations induced by histamine, ATP, nitric oxide, cell lymphoma by enhancing Noxa-mediated activation of Bak.” the nitric oxide donors S-nitrosoglutathione, S-nitroso-N-acetyl- Blood 109: 4441‑4449 (2007). D,L-penicillamine, and spermine NONOate, as well as the direct • Obatoclax augmented tumor necrosis factor-related apoptosis- sGC-stimulant YC-1 but not relaxations induced by papaverine inducing ligand (TRAIL)-mediated apoptosis, possibly by and atriopeptin II. Feelisch, M. et al., “The Soluble Guanylyl releasing Bak and Bim from Bcl-2/Bcl-xL or Mcl-1 proteins in Cyclase Inhibitor 1H-[1,2,4]Oxadiazolo[4,3,-a]quinoxalin-1-one human pancreatic cancer cells. Huang, S. et al., “BH3 mimetic Is a Nonselective Heme Protein Inhibitor of Nitric Oxide Synthase obatoclax enhances TRAIL-mediated apoptosis in human and Other Cytochrome P-450 Enzymes Involved in Nitric Oxide pancreatic cancer cells.” Clin. Cancer Res. 15: 150‑159 (2009). Donor Bioactivation.” Mol. Pharmacol. 56: 243‑253 (1999). • Obatoclax inhibited influenza A virus (IAV) uptake • ODQ decreased the minimum alveolar anesthesia concentration and demonstrated broad-spectrum antiviral activity. for isoflurane anesthesia in Sprague-Dawley rats but did not Denisova, O.V. et al., “Obatoclax, saliphenylhalamide, affect their arterial blood pressure or heart rate. Cechova, S. and and gemcitabine inhibit influenza A virus infection.” Pajewski, T.N., “The soluble guanylyl cyclase inhibitor ODQ, J. Biol. Chem. 287: 35324‑35332 (2012). 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, dose-dependently reduces the threshold for isoflurane anesthesia in rats.” • Related CAS number: 803712-67-6 for the free base. Anesth. Analg. 99: 752‑757 (2004). • Sold for laboratory or manufacturing purposes only; not for • The effects of both nitric oxide and ODQ on sGC can be human, veterinary, food, or household use. inhibited by myoglobin. Nitric oxide and ODQ exert only • This product is offered for R&D use in accordance with (i) 35 minor effects in cardiomyocytes where myoglobin is abundant USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese but they show strong effects in aortic tissue where there is Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent very little myoglobin. Wegener, J.W. et al., “Failure of 1H- Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to inhibit Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) soluble guanylyl cyclase in rat ventricular cardiomyocytes.” and other common law exemptions of Canadian patent law; (vi) Br. J. Pharmacol. 127: 693‑700 (1999). Section 68B of the Patents Act of 1953 in New Zealand together • ODQ inhibited sGC competitively with nitric oxide. The with the amendment of same by the Statutes Amendment Bill of inhibition resulted in an apparently irreversible oxidation of the 2002; (vii) such related legislation and/or case law as may be or prosthetic heme group. Schrammel, A. et al., “Characterization become applicable in the aforementioned countries; and (viii) such of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme- similar laws and rules as may apply in various other countries. site inhibitor of nitric oxide-sensitive guanylyl cyclase.” • Not available in some countries; not available to some institutions; Mol. Pharmacol. 50: 1‑5 (1996). not available for some uses. • Sold for laboratory or manufacturing purposes only; not for CH 3 human, veterinary, food, or household use. O O O NN N N H CH . CH O S H 3 4 3 N N

H C 3

76 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

O-2220 Okadaic Acid, Free Acid, >98% O-7519 Okadaic Acid, Potassium Salt, >98% [Halochondrine A] [Halochondrine A]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 50 µg 48 33 29 4,500 50 µg 48 33 29 4,500 100 µg 85 59 52 8,000 100 µg 85 59 52 8,000 300 µg 228 159 138 21,500 300 µg 228 159 138 21,500 1 mg 595 415 361 56,200 1 mg 595 415 361 56,200 2 mg 998 696 605 94,200 2 mg 998 696 605 94,200 5 mg 1990 1387 1206 187,800 5 mg 1990 1387 1206 187,800 NOTE: Euro, Pound and Yen prices are revised regularly. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Please visit www.LCLabs.com for our current prices.

M.W. 805.00 c44H68O13 M.W. 843.09 c44H67O13•K [209266-79-5] [78111-17-8] M.I. 14: 6819 WARNING: Highly irritant to skin and mucous membranes. WARNING: Highly irritant to skin and mucous SPECIAL HAZARD: TUMOR PROMOTER. Gloves and membranes. SPECIAL HAZARD: TUMOR PROMOTER. mask should be worn when using this compound. Care Gloves and mask should be worn when using this must be taken to prevent contact through all routes of compound. Care must be taken to prevent contact exposure. through all routes of exposure. Storage: Store at or below -20 °C. Solubility: Soluble in Storage: Store at or below -20 °C. Solubility: Soluble in DMSO or ethanol. Disposal: A DMSO or ethanol. Disposal: A • Salt form of okadaic acid, with somewhat greater stability than the • Potent inhibitor of protein phosphatases, especially the PP-1 free acid when stored in organic solvents. See notes on stability and PP-2A classes, in numerous cell types. Cohen, P. et al. in the entry for okadaic acid free acid (Cat. No. O-2220 on Trends Biochem. Sci. 15: 98-102 (1990). page 76). • Non-phorbol type tumor promoter. Suganuma, M. et al. • Please request Technical Note #18 for additional information. Proc. Natl. Acad. Sci. USA 85: 1768-1771 (1988). • Sold for laboratory or manufacturing purposes only; not for • Please request Technical Note #18 for additional information. human, medical, veterinary, food, or household use. • Important Notes on Stability: O OH 1. We believe this product and the three okadaic acid salts H H below, as shipped from our inventory, are the purest and + - O O K O most stable okadaic acid products available anywhere. In OH O O O contrast, material from other vendors is often degraded and OH H O O quite impure. Long-term stability of our four okadaic acid OH products in their unopened ampules is excellent (one year or more). O-5857 Okadaic Acid, Sodium Salt, >98% 2. All four okadaic acid products must first be dissolved in an [Halochondrine A] organic solvent to prepare stock solutions. The okadaic acid molecule is large and somewhat hydrophobic, and material Size US$ ¤ £ ¥ cannot be reliably dissolved out of the ampule with purely 50 g 48 33 29 4,500 aqueous solutions. We understand that some practitioners µ use mixed aqueous/organic solvents to dissolve material out 100 µg 85 59 52 8,000 of the ampules, but we have not tested the efficacy of this 300 µg 228 159 138 21,500 approach ourselves. 1 mg 595 415 361 56,200 3. Solutions of the free acid form of okadaic acid in organic 2 mg 998 696 605 94,200 solvents are distinctly less stable, even in the freezer, than 5 mg 1990 1387 1206 187,800 those made from the three salt forms listed below. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 4. Once diluted into aqueous media (and assuming equal starting purities), the information available to us indicates M.W. 826.98 c44H67O13•Na [209266-80-8] that all four forms of okadaic acid show comparable stability. WARNING: Highly irritant to skin and mucous membranes. 5. The biological activity of all four products is identical for SPECIAL HAZARD: TUMOR PROMOTER. Gloves and the okadaic acid portion, but obviously the counter-ions mask should be worn when using this compound. Care themselves may affect ion-sensitive experimental systems. must be taken to prevent contact through all routes of 6. In summary: ignoring the counter-ions, all four forms of exposure. okadaic acid are biologically equivalent and equally useful Storage: Store at or below -20 °C. Solubility: Soluble in if made up as a stock solution in an organic solvent and used DMSO or ethanol. Disposal: A within a fews days. If freezer storage of an organic solvent- • Salt form of okadaic acid, with somewhat greater stability than based stock solution of okadaic acid is anticipated to extend the free acid when stored in organic solvents. See notes on beyond a week or so, we recommend a salt form rather than stability in the entry for okadaic acid free acid (Cat. No. the free acid. O-2220 on page 76). • Sold for laboratory or manufacturing purposes only; not for • Please request Technical Note #18 for additional information. human, medical, veterinary, food, or household use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. O OH H H O O HO O OH H H OH O O O + - O O OH H O O Na O OH O O O OH OH H O O OH

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 77 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Other CAS numbers previously assigned to olaparib, namely O-9201 Olaparib, >99% 894104-70-2, 937799-91-2, and 1021843-02-6, have been deleted [AZD-2281] [KU-59436] by CAS and are no longer in use. • Sold for laboratory or manufacturing purposes only; not for Size US$ ¤ £ ¥ human, medical, veterinary, food, or household use. 10 mg 49 38 32 5,500 • This product is offered for R&D use in accordance with (i) 35 25 mg 68 53 45 7,600 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 50 mg 99 77 65 11,100 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 100 mg 166 128 110 18,600 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 250 mg 225 174 149 25,200 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 500 mg 348 269 230 38,900 and other common law exemptions of Canadian patent law; (vi) 1 g 647 500 428 72,300 Section 68B of the Patents Act of 1953 in New Zealand together 2 g 1190 920 787 133,000 with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or 5 g 1875 1449 1240 209,600 become applicable in the aforementioned countries; and (viii) such NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. similar laws and rules as may apply in various other countries. M.W. 434.46 c H FN O [763113-22-0] • Not available in some countries; not available to some institutions; 24 23 4 3 not available for some uses. M.I. 14: 10415 O Storage: Store at or below -20 ºC. Solubility: Soluble in F DMSO at 33 mg/mL; soluble in ethanol at 1.7 mg/mL with N

slight warming; very poorly soluble in water; maximum N solubility in plain water is estimated to be about 10‑20 µM; buffers, serum, or other additives may increase or O decrease the aqueous solubility. Disposal: A N NH • Olaparib is a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor and an anti-cancer drug being tested in patients with mutations in O the genes BRCA1 or BRCA2. • PARP1 acts as a critical molecule in the repair of DNA single- Oncovin – see its active ingredient, namely Vincristine, strand breaks (SSBs) and plays an important role in maintaining Sulfate Salt (Cat. No. V-8400 on page 122). DNA integrity. de Murcia, J. et al., “Requirement of poly(ADP- Onkovin – see its active ingredient, namely Vincristine, ribose) polymerase in recovery from DNA damage in mice and in Sulfate Salt (Cat. No. V-8400 on page 122). cells.” Proc. Natl. Acad. Sci. USA 94: 7303-7307 (1997). Onsenal — see Celecoxib (Cat. No. C-1502 on page 20). • PARP inhibitors inhibit PARP1 during S-phase and induce inactivation of SSB repair and thus cause DNA double-strand OSI 906AA — see Linsitinib, Free Base (Cat. No. L-5814 on page 65). breaks, which induces BRCA-deficient cancer cell apoptosis. Bryant, H.E. et al., “Specific killing of BRCA2-deficient tumours OSI-774 — see Erlotinib, Free Base (Cat. No. E-4997 on page 37) and with inhibitors of poly(ADP-ribose) polymerase.” Erlotinib, Hydrochloride Salt (Cat. No. E-4007 on page 38). Nature 434: 913-917 (2005). Farmer, H. et al., “Targeting OSI-906 — see Linsitinib, Free Base (Cat. No. L-5814 on page 65). the DNA repair defect in BRCA mutant cells as a therapeutic strategy.” Nature 434: 917-921 (2005). O-5679 OSU-03012, Hydrochloride Salt, >99% • The PARP inhibitor olaparib was tested in a genetically engineered mouse model for BRCA1-associated breast cancer. Olaparib Size US$ ¤ £ ¥ inhibited tumor growth and significantly improved survival 5 mg 48 37 32 4,800 without signs of toxicity. Rottenberg, S. et al., “High sensitivity 10 mg 84 64 55 8,400 of BRCA1-deficient mammary tumors to the PARP inhibitor 25 mg 162 124 106 16,100 AZD2281 alone and in combination with platinum drugs.” 50 mg 298 228 196 29,600 Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008). 100 mg 545 417 358 54,200 • Long-term treatment with olaparib caused the development of 300 mg 1290 988 847 128,300 drug resistance, which was induced by up-regulation of Abcb1a/b NOTE: Euro, Pound and Yen prices are revised regularly. genes encoding P-glycoprotein efflux pumps. The resistance Please visit www.LCLabs.com for our current prices. to olaparib could be overcome by tariquidar, a P-glycoprotein M.W. 496.91 c H F N O •HCl inhibitor. Rottenberg, S. et al., “High sensitivity of BRCA1- 26 19 3 4 [1471979-81-3] deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.” Proc. Natl. Acad. Storage: Store at or below -20 °C. Solubility: Soluble in Sci. USA 105: 17079-17084 (2008). DMSO at 60 mg/mL; soluble in ethanol at 15 mg/mL with • Combination treatment using olaparib with cisplatin or carboplatin warming; very poorly soluble in water; maximum solubility improved the recurrence-free and overall survival in a murine in plain water is estimated to be about 10-20 µM; buffers, model, indicating that olaparib enhances the effect of these serum, or other additives may increase or decrease the DNA-damaging agents. Rottenberg, S. et al., “High sensitivity aqueous solubility. Disposal: A of BRCA1-deficient mammary tumors to the PARP inhibitor • Inhibitor of phosphoinositide-dependent kinase-1. OSU-03012 AZD2281 alone and in combination with platinum drugs.” inhibited both recombinant 3-phosphoinositide-dependent Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008). kinase-1 activity and PC-3 cell viability with similar IC50 values • Olaparib inhibited the growth of BRCA2-deficient versus of ~5 µM. Exposure of PC-3 cells to OSU-03012 led to Akt BRCA2-proficient mammary tumor cells. Combination treatment dephosphorylation and inhibition of p70 S6 kinase activity. of olaparib and cisplatin had a synergistic cytotoxicity against Moreover, overexpression of constitutively active forms of PDK-1 BRCA2-deficient cells but not against BRCA2-proficient control and Akt partially protected against OSU-03012-induced apoptosis. cells. Evers, B. et al., “Selective inhibition of BRCA2-deficient Screening in a panel of 60 cell lines and more extensive testing in mammary tumor cell growth by AZD2281 and cisplatin.” PC-3 cells indicated that the mean concentration for total growth Clin. Cancer Res. 14: 3916-3925 (2008). inhibition by OSU-03012 was approximately 3 µM. Zhu J. et al., “From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class

78 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

of 3-Phosphoinositide-Dependent Protein Kinase-1 Inhibitors.” Oxalato(1R,2R-cyclohexanediamine)platinum(II) — Cancer Res. 64: 4309-4318 (2004). see Oxaliplatin (Cat. No. O-7111 on page 79). • OSU-03012 showed no increased resistance in the mutant cells E255K T315I Oxalatoplatin — see Oxaliplatin (Cat. No. O-7111 on page 79). Ba/F3p210 and Ba/F3p210 , with an IC50 of 5 µM

irrespective of mutations. Nevertheless, in the presence of OSU- Oxalatoplatinum — see Oxaliplatin (Cat. No. O-7111 on page 79). 03012 the susceptibility of these mutant cells to imatinib-induced apoptosis was significantly enhanced. Together these data provide O-7111 Oxaliplatin, >99%

a novel therapeutic strategy to overcome imatinib mesylate [Dacplat] [Eloxatin] [Eloxatine] [Elplat] [Foloxatine] resistance, especially with the Abl mutant T315I. Tseng P.H. et al., “Synergistic interactions between imatinib mesylate and the [Oxalato(1R,2R-cyclohexanediamine)platinum(II)] novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012, [Oxalatoplatin] [Oxalatoplatinum] [RP 54780] Hydrochloride Salt in overcoming imatinib mesylate resistance.” [Transplatin] Blood 105: 4021-4027 (2005). Size US$ ¤ £ ¥ • The dose of OSU-03012, Hydrochloride Salt to induce 50% 300 mg 99 81 64 7,900 chronic lymphocytic leukemia cell death (LC50) at 24 hours was 7.1 µM. Additionally, OSU-03012 mediates apoptosis by 500 mg 145 111 91 11,800 activation of the intrinsic, mitochondrial pathway of apoptosis 1 g 229 175 144 18,700 but also activates alternative cell death pathways that are caspase 2 g 414 316 261 33,800 independent. Johnson A.J. et al., “A novel celecoxib derivative, 5 g 695 531 438 56,800 OSU-03012, Hydrochloride Salt, induces cytotoxicity in primary NOTE: Euro, Pound and Yen prices are revised regularly. CLL cells and transformed B-cell lymphoma cell line via a Please visit www.LCLabs.com for our current prices. caspase- and Bcl-2–independent mechanism.” M.W. 397.29 C H N O Pt [61825-94-3] Blood 105: 2504-2509 (2005). 8 14 2 4 [63121-00-6] M.I. 14: 6912 • OSU-03012 inhibited phosphorylated Akt (P-Akt) and its downstream signalling through 4E binding protein and glycogen Storage: Store at or below -20 ºC. Solubility: Soluble in synthase kinase at concentrations well below that of celecoxib. water at 4 mg/mL and DMSO at 20 mg/mL; very slightly Disruption of P-Akt was followed by induction of apoptosis and soluble in methanol; insoluble in ethanol. Disposal: A more than 90% cell death. Kucab J.E. et al., “Celecoxib analogues • Oxaliplatin is a a third-generation, diaminocyclohexane-containing disrupt Akt signaling, which is commonly activated in primary platinum anti-cancer drug. It is typically used in combination with breast tumours.” Breast Cancer Res. 7: R796–R807 (2005). fluorouracil (5-FU) and leucovorin, known as FOLFOX, for the • OSU-03012 caused a dose-dependent induction of cell death that treatment of colorectal cancer. The leucovorin-modulated single- was not altered by p53 mutation or expression of ERBB1 vIII. agent 5-FU regimens achieved a median overall survival of 15 OSU-03012 promotes glioma cell killing that is dependent on months or less. Combination regimens of FOLFOX consistently endoplasmic reticulum stress, lysosomal dysfunction, and BID- lead to median survivals in the 15 to 20-month range. Goldberg, dependent release of AIF from mitochondria, and whose lethality R.M., “Therapy for Metastatic Colorectal Cancer.” The Oncologist is enhanced by irradiation or by inhibition of protective signaling 11: 981-987 (2006). pathways. Yacoub A. et al., “OSU-03012 promotes caspase- • Oxaliplatin has different antitumor spectrum, mechanisms independent but PERK-, cathepsin B-, BID-, and AIF-dependent of action, and resistance from the other platinum-containing killing of transformed cells.” Mol. Pharmacol. 70: 589-603 (2006). compounds, notably cisplatin. Raymond, E. et al., “Cellular and • This OSU-03012 product is the hydrochloride salt, whose CAS molecular pharmacology of oxaliplatin.” Mol. Cancer Ther. 1: number is given above. The CAS number for the free base is 227-235 (2002). 742112-33-0. • The anticancer activity and the antitumor specificity of oxaliplatin • Sold for laboratory or manufacturing purposes only; not for mainly depend on human organic cation transporters (OCT) 1 human, medical, veterinary, food, or household use. and OCT2. Zhang, S. et al., “Organic cation transporters are determinants of oxaliplatin cytotoxicity.” Cancer Res. 66: 8847- • This product is offered for R&D use in accordance with (i) 35 8857 (2006). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • The oxaliplatin cytotoxicity depends on MKK7/JNK, while Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. SEK1 might be involved in hypoxic resistance to oxaliplatin. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Vasilevskaya, I.A. et al., “Disruption of signaling through SEK1 and other common law exemptions of Canadian patent law; (vi) and MKK7 yields differential responses in hypoxic colon cancer Section 68B of the Patents Act of 1953 in New Zealand together cells treated with oxaliplatin.” Mol. Pharmacol. 74: 246-254 with the amendment of same by the Statutes Amendment Bill of (2008). 2002; (vii) such related legislation and/or case law as may be or • Oxaliplatin is the active ingredient in the drug sold under the become applicable in the aforementioned countries; and (viii) such trade name Eloxatin®. The drug is currently approved in at least similar laws and rules as may apply in various other countries. one country for use in patients with colorectal cancer. NOTE: the • Not available in some countries; not available to some institutions; oxaliplatin sold by LC Laboratories is NOT Eloxatin® and is NOT not available for some uses. for human use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese .HCl Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. F C 3 N N Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) O and other common law exemptions of Canadian patent law; (vi) NH 2 Section 68B of the Patents Act of 1953 in New Zealand together N with the amendment of same by the Statutes Amendment Bill of H 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one — similar laws and rules as may apply in various other countries. see ODQ, Free Base (Cat. No. O-1666 on page 76).

O-5679-2010-03-23-ecg-SKCLCrev.SKC WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 79 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; O not available for some uses. H C 3 O H C O O O 3 CH 3 OH CH NH O 3 H N NH 2 2 OH Pt HO O O O O O O

O O CH O 3 22-Oxovincaleukoblastine sulfate – see Vincristine, Sulfate Salt (Cat. No. V-8400 on page 122). p53 Activator III – see RITA (Cat. No. R-7117 on page 98). P-3703 Panobinostat, Free Base, >99% P-9600 Paclitaxel, >99.5% [Faridak] [LBH 589] [NVP-LBH-589] [Taxol] Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 5 mg 42 32 28 4,700 100 mg 39 30 26 4,400 10 mg 61 47 40 6,800 250 mg 78 60 52 8,700 25 mg 92 71 61 10,300 500 mg 119 92 79 13,300 50 mg 129 100 85 14,400 1 g 210 162 139 23,500 100 mg 210 162 139 23,500 2 g 382 295 253 42,700 200 mg 398 308 263 44,500 5 g 865 669 572 96,700 250 mg 462 357 305 51,700 10 g 1560 1206 1031 174,400 300 mg 516 399 341 57,700 NOTE: Euro, Pound and Yen prices are revised regularly. 500 mg 798 617 528 89,200 Please visit www.LCLabs.com for our current prices. 1 g 1145 885 757 128,000 NOTE: Euro, Pound and Yen prices are revised regularly. M.W. 853.91 c47H51NO14 [33069-62-4] Please visit www.LCLabs.com for our current prices. M.I. 14: 6982 M.W. 349.43 c H N O [404950-80-7] Storage: Store at or below -20 ºC. Solubility: Soluble in 21 23 3 2 DMSO (up to about 200 mg/mL) or ethanol (up to about Storage: Store at or below -20 ºC. Solubility: Soluble in 40 mg/mL). Disposal: A DMSO at 200 mg/mL; soluble in ethanol at 5 mg/mL with warming; very poorly soluble in water; maximum solubility • Antitumor and antileukemic agent isolated from the bark of the in plain water is estimated to be about 20-50 µM; buffers, yew tree, Taxus brevifolia. Wani, M.C. et al., “Plant antitumor serum, or other additives may increase or decrease the agents. VI. The isolation and structure of taxol, a novel aqueous solubility. Disposal: A antileukemic and antitumor agent from Taxus brevifolia.” J. of Amer. Chem. Soc. 93: 2325-2327 (1971). McGuire, W.P. et al., • Panobinostat, a histone deacetylase inhibitor, is being tested in “Taxol: a unique antineoplastic agent with significant activity in humans against cutaneous T cell lymphoma, prostate cancer, advanced ovarian epithelial neoplasms.” Ann. Int. Med. 111: 273- myelodysplastic syndromes, breast cancer, chronic myelogenous 279 (1989). leukemia, and other types of malignant disease. • Panobinostat inhibited histone deacetylase and induced acetylation • Binds to β-tubulin and promotes the assembly of microtubules that resist depolymerization preventing normal cell division. Rowinsky, of histone H3 and alpha-tubulin protein in human umbilical E.K. et al., “Taxol: a novel investigational antimicrotubule vein endothelial cells (HUVEC), which resulted in induction of agent.” J. Natl. Cancer Inst. 82: 1247-1259 (1990). Parekh, H. G(2)-M cell cycle arrest and inhibition of HUVEC proliferation and Simpkins, H., “The transport and binding of taxol.” Gen. and viability. Panobinostat at noncytotoxic concentrations Pharmacol. 29: 167-172 (1997). Jordan, A. et al., “Tubulin as a inhibited endothelial tube formation, Matrigel invasion, AKT target for anticancer drugs: agents which interact with the mitotic activity, extracellular signal-regulated kinase 1/2 phosphorylation spindle investigational antimicrotubule agent.” Med. Res. Rev. 18: and chemokine receptor CXCR4 expression. It aslo reduced 259-296 (1998). angiogenesis and PC-3 tumor growth in mice. Qian D.Z. et al., “Targeting tumor angiogenesis with histone deacetylase inhibitors: ·• Induces apoptosis through a JNK-dependent pathway in the early the hydroxamic acid derivative LBH589.” Clin. Cancer Res. phase followed by a JNK-independent pathway that results in Bcl- 12: 634‑642 (2006). 2 phosphorylation. Wang, T.H. et al., “Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun • After 3 days of incubation, panobinostat inhibited the proliferation of 7 of 8 tested pancreatic cell lines with a mean IC of 0.09 N-termnial kinase (JNK)-dependent and -independent pathways 50 M. Only cell line Capan-2 demonstrated an IC value >1 M. in overian cancer cells.” J. Biol. Chem. 274: 8208-8216 (1999). µ 50 µ Shtil, A.A. et al., “Differential regulation of mitogen-activated Inhibition of cell growth was more marked if the incubation time protein kinases by microtubule-binding agents in human breast was extended to 6 days. In vivo, panobinostat alone significantly cancer cells.” Oncogene 18: 377-384 (1999). Srivastava, R.K. decreased tumor mass and augmented the efficacy of gemcitabine. et al., “Involvement of microtubules in the regulation of Bcl2 Haefner M. et al., “Experimental treatment of pancreatic cancer phosphorylation and apoptosis through cyclic AMP-dependent with two novel histone deacetylase inhibitors.” protein kinase.” Mol. Cell. Biol. 18: 3509-3517 (1998). Torres, K. World J. Gastroenterol. 14: 3681-3692 (2008). and Horwitz, S.B., “Mechanisms of Taxol-induced cell death are • In addition to acetylation of histone H3 and H4, panobinostat also concentration dependent.” Cancer Res. 58: 3620-3626 (1998). induces acetylation of heat shock protein 90 (hsp90). Cotreatment • Paclitaxel is the active ingredient in the drug sold under the trade with panobinostat and the hsp90 inhibitor 17-allylamino-17- name Taxol®. NOTE: the paclitaxel sold by LC Laboratories is demethoxygeldanamycin (17-AAG) caused synergistic apoptosis NOT Taxol® and is NOT for human use. of acute leukemia MV4-11 and K562 cells. This combination treatment induced apoptosis of the imatinib mesylate (IM)- • Sold for laboratory or manufacturing purposes only; not for refractory leukemia cells expressing Bcr-Abl with the T315I human, medical, veterinary, food, or household use. mutation. The cotreatment also brought about more apoptosis of IM-resistant primary chronic myeloid leukemia blast crisis (CML-

80 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

BC) and acute myeloid leukemia (AML) cells with an activating mutation of FLT-3 than treatment with either drug alone. George P. P-6706 Pazopanib, Free Base, >99% et al., “Combination of the histone deacetylase inhibitor LBH589 Synonyms: [GW-786034] and the hsp90 inhibitor 17-AAG is highly active against human Related Terms: [Armala] [Votrient] CML-BC cells and AML cells with activating mutation of FLT-3.” Blood 105: 1768-1776 (2005). Size US$ ¤ £ ¥ • Treatment with LBH589 for 48 hours potently inhibited MTT 25 mg 59 46 39 6,600 uptake. IC50 values for these multiple myeloma cell lines 50 mg 84 65 56 9,400 were 5.7 nM (MM1S), 6.5 nM (MM1R), 8.1 nM (U266), 100 mg 129 100 85 14,400 24 nM (U266LR7), and 45.5 nM (U266DOX4). Maiso P. 200 mg 198 153 131 22,100 et al., “The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance.” Cancer Res. 300 mg 272 210 180 30,400 66: 5781‑5789 (2006). 500 mg 385 298 255 43,000 • Panobinostat is well tolerated and induces clinical responses 1 g 545 421 360 60,900 in cutaneous T-cell lymphoma (CTCL) patients. Ellis L. et al., 2 g 934 722 617 104,400 “Histone deacetylase inhibitor panobinostat induces clinical 5 g 1660 1283 1097 185,600 responses with associated alterations in gene expression NOTE: Euro, Pound and Yen prices are revised regularly. profiles in cutaneous T-cell lymphoma.” Clin. Cancer Res. Please visit www.LCLabs.com for our current prices. 14: 4500‑4510 (2008). M.W. 437.52 C21H23N7O2S [444731-52-6] • QTcF prolongation was one of the dose-limiting toxicities Storage: Store at or below -20 ºC. Solubility: Soluble of panobinostat but was asymptomatic and was reversed in DMSO at 8.3 mg/mL with slight warming; very poorly after panobinostat discontinuation. Giles F. et al., “A phase I soluble in ethanol; very poorly soluble in water; maximum study of intravenous LBH589, a novel cinnamic hydroxamic solubility in plain water is estimated to be about 10‑20 µM; acid analogue histone deacetylase inhibitor, in patients with buffers, serum, or other additives may increase or refractory hematologic malignancies.” Clin. Cancer Res. decrease the aqueous solubility. Disposal: A 12: 4628‑4635 (2006). • Pazopanib is an oral, second-generation, potent and selective • Sold for laboratory or manufacturing purposes only; not for multi-targeted tyrosine kinase inhibitor that targets vascular human, medical, veterinary, food, or household use. endothelial growth factor receptor (VEGFR), platelet-derived • This product is offered for R&D use in accordance with (i) 35 growth factor receptor and c-kit, key proteins responsible for USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese tumor growth and angiogenesis. Pazopanib showed good potency Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent against all of the human VEGFRs and some related tyrosine Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. receptor kinases in vitro, and demonstrated antitumor activity Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) against renal cell carcinoma (RCC), and breast, lung, and other and other common law exemptions of Canadian patent law; (vi) related cancers. Sloan, B. and Scheinfeld, N.S., “Pazopanib, a Section 68B of the Patents Act of 1953 in New Zealand together VEGF receptor tyrosine kinase inhibitor for cancer therapy.” with the amendment of same by the Statutes Amendment Bill of Curr. Opin. Investig. Drugs 9: 1324-1335 (2008). 2002; (vii) such related legislation and/or case law as may be or • Preclinical evaluation has demonstrated excellent anti-tumor and become applicable in the aforementioned countries; and (viii) such anti-angiogenic activity. A Phase II clinical trial of pazopanib in similar laws and rules as may apply in various other countries. untreated or cytokine/bevacizumab pretreated renal cell carcinoma • Not available in some countries; not available to some institutions; has revealed promising activity with a favorable toxicity profile. not available for some uses. Sonpavde, G. et al., “Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal O cell carcinoma.” Expert Opin. Investig. Drugs 17: 253-261 (2008). H OH N • Orally administered Pazopanib has good bioavailability N H to the retina/choroid and strongly suppresses choroidal neovascularization (CNV) in a dose-dependent manner in mice. Takahashi, K. et al., “Suppression and regression of choroidal N CH 3 neovascularization by the multitargeted kinase inhibitor H pazopanib.” Arch. Ophthalmol. 127: 494-499 (2009). Patupilone — see Epothilone B, P-3703Free Base • Pazopanib inhibits in vivo tumor cell growth in a mouse xenograft (Cat. No. E-5500 on page 36). model of human multiple myeloma (MM) associated with increased MM cell apoptosis, prolonged survival, and decreased P-3703 2010-02-12 HZ_RevSKC.skc angiogenesis. Podar, K. et al., “The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma.” Proc. Natl. Acad. Sci. USA 103: 19478-19483 (2006). • Pazopanib is the active ingredient in the drug product sold under the trade names Armala® and Votrient®. This drug is currently approved in at least one country for use in patients with advanced renal cell carcinoma (RCC) and for use in patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. THE PAZOPANIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ARMALA® NOR VOTRIENT® AND IS NOT FOR HUMAN USE. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6)

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 81 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together P-3333 PD 173074, Free Base, >99% with the amendment of same by the Statutes Amendment Bill of Size US$ ¤ £ ¥ 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such 5 mg 29 22 18 2,300 similar laws and rules as may apply in various other countries. 10 mg 49 37 31 3,800 • Not available in some countries; not available to some institutions; 25 mg 98 73 63 7,600 not available for some uses. 50 mg 144 108 92 11,200 100 mg 226 169 144 17,500 200 mg 399 298 255 31,000 NH N N N 250 mg 486 363 310 37,700 N N 500 mg 928 693 592 72,100 1 g 1670 1247 1065 129,700 O S NH NOTE: Euro, Pound and Yen prices are revised regularly. O 2 Please visit www.LCLabs.com for our current prices. M.W. 523.67 C H N O [219580-11-7] P-4313 PD 98059, >99% 28 41 7 3 Storage: Store at or below -20 ºC. Solubility: Soluble in [2'-Amino-3'-methoxyflavone] DMSO at 100 mg/mL; soluble in ethanol at 200 mg/mL; Size US$ ¤ £ ¥ very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 µM; buffers, serum, 25 mg 64 46 38 8,500 or other additives may increase or decrease the aqueous 50 mg 111 80 65 14,800 solubility. Disposal: A 100 mg 198 143 117 26,300 • PD 173074 selectively inhibits the tyrosine kinase activities of the 200 mg 368 265 217 48,900 FGF and VEGF receptors. 250 mg 425 306 250 56,500 • PD 173074 inhibited the kinase activity of FGFR1 with an IC 300 mg 447 322 263 59,400 50 of 25 nM in vitro, while inhibiting Src, the receptors for insulin, 500 mg 699 504 412 92,900 epidermal growth factor (EGF) and PDGF, and several serine/ 1 g 1335 962 786 177,400 threonine kinases with 1000-fold or higher IC50 values. PD 173074 NOTE: Euro, Pound and Yen prices are revised regularly. was an ATP-competitive inhibitor of FGFR1, with a Ki of around Please visit www.LCLabs.com for our current prices. 40 nM. PD 173074 inhibited autophosphorylation of FGFR1 and M.W. 267.28 C16H13NO3 [167869-21-8] VEGFR2 in a dose-dependent manner with IC50s in the range of Storage: Store at or below -20 °C. Solubility: Soluble in 1-5 nM and 100-200 nM, respectively. Mice treated daily with DMSO at 25 mg/mL; soluble in ethanol at 1 mg/mL with PD 173074 exhibited dose-dependent inhibition of FGF-induced warming; very poorly soluble in water; maximum solubility and VEGF-induced neovascularization. However, PD 173074 was in plain water is estimated to be about 50-100 µM; buffers, somewhat less effective in blocking VEGF-induced than FGF- serum, or other additives may increase or decrease the induced angiogenesis. Mohammadi, M. et al., “Crystal structure aqueous solubility. Appearance: Pale-yellow powder. of an angiogenesis inhibitor bound to the FGF receptor tyrosine Disposal: A kinase domain.” EMBO J. 17: 5896‑5904 (1998). • Potent, selective and cell-permeable inhibitor of MAP kinase • PD 173074 inhibited cell proliferation of two low-grade, kinase (also known as MAPK/ERK kinase or MEK kinase). noninvasive human bladder urothelial carcinoma (UC) cell Inhibits phosphorylation of MAP kinase by MAP kinase kinase. lines, UM-UC-14 and MGHU3, which expressed mutated FGFR3 protein. However, the other six cell lines expressing PD 98059 does not inhibit MAP kinase itself. IC50 values for PD 98059-induced effects are in the 1-20 µM range for many assays; wild-type FGFR3 or without FGFR3 expression were resistant it is somewhat weaker in inhibiting cell growth in monolayers or to PD 173074 treatment. In the mouse xenograft models agar for some cell lines. Dudley, D.T. et al. Proc. Natl. Acad. subcutaneously transplanted with these two cell lines, orally Sci. USA 92: 7686-7689 (1995). Pang, L. et al. J. Biol. Chem. administered PD 173074 suppressed tumor growth and induced 270: 13585-13588 (1995). Waters, S.B. et al. J. Biol. Chem. apoptosis. Miyake, M. et al., “1-tert-butyl-3-[6-(3,5-dimethoxy- 270: 20883-20886 (1995). Langlois, W.J. et al. J. Biol. Chem. phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin- 270: 25320-25323 (1995). Alessi, D.R. et al. J. Biol. Chem. 7-yl]-urea (PD 173074), a selective tyrosine kinase inhibitor 270: 27489-27494 (1995). of fibroblast growth factor receptor-3 (FGFR3), inhibits cell proliferation of bladder cancer carrying the FGFR3 gene • Sold for laboratory or manufacturing purposes only; not for mutation along with up-regulation of p27/Kip1 and G1/G0 arrest.” human, medical, veterinary, food, or household use. J. Pharmacol. Exp. Ther. 332: 795‑802 (2010). • The FGFR1 inhibitor PD 173074 dose-dependently inhibited

O FGF-2 promotion of granule neuron survival under low-potassium, OMe serum-free conditions with IC50 of 12 nM, when added together

NH2 with FGF-2 for a 24-h pretreatment prior to potassium withdrawal. Skaper, S.D. et al., “The FGFR1 inhibitor PD 173074 selectively O and potently antagonizes FGF-2 neurotrophic and neurotropic effects.” J. Neurochem. 75: 1520‑1527 (2000). PD 123654 — see CI-994, Free Base (Cat. No. C-2606 on page 21). • PD 173074 inhibited the proliferation and clonogenic growth of small cell lung cancer cell lines H-510 and H-69 in vitro and in vivo. It also prevented FGF-2-induced chemoresistance. These effects correlated with the inhibition of both FGFR1 and FGFR2 transphosphorylation. Pardo, O.E. et al., “The fibroblast growth factor receptor inhibitor PD 173074 blocks small cell lung cancer growth in vitro and in vivo.” Cancer Res. 69: 8645‑8651 (2009). • PD 173074 inhibited the growth of glioblastoma cells in vitro. Loilome, W. et al., “Glioblastoma cell growth is suppressed by disruption of Fibroblast Growth Factor pathway signaling.” J. Neurooncol. 94: 359‑366 (2009).

82 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Sold for laboratory or manufacturing purposes only; not for independent caspase-8 activation. Meng, X.W. et al., “Central Role human, veterinary, food, or household use. of Fas-associated Death Domain Protein in Apoptosis Induction • This product is offered for R&D use in accordance with (i) 35 by the Mitogen-activated Protein Kinase Inhibitor CI-1040 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese (PD184352) in Acute Lymphocytic Leukemia Cells in vitro.” J. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Biol. Chem. 278: 47326-47339 (2003). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • However, PD184352 suffered from poor pharmacokinetics because Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) of its low solubility and rapid clearance. Barrett, S.D. et al., “The and other common law exemptions of Canadian patent law; (vi) discovery of the benzhydroxamate MEK inhibitors CI-1040 and Section 68B of the Patents Act of 1953 in New Zealand together PD 0325901.” Bioorg. Med. Chem. Lett. 18: 6501-6504 (2008). with the amendment of same by the Statutes Amendment Bill of • Sold for laboratory or manufacturing purposes only; not for 2002; (vii) such related legislation and/or case law as may be or human, medical, veterinary, food, or household use. become applicable in the aforementioned countries; and (viii) such • This product is offered for R&D use in accordance with (i) 35 similar laws and rules as may apply in various other countries. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Not available in some countries; not available to some institutions; Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent not available for some uses. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. OCH Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 3 and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together H C with the amendment of same by the Statutes Amendment Bill of 3 OCH N 3 2002; (vii) such related legislation and/or case law as may be or H C N H 3 N N CH become applicable in the aforementioned countries; and (viii) such N N 3 CH 3 similar laws and rules as may apply in various other countries. H O N CH 3 • Not available in some countries; not available to some institutions; H not available for some uses.

P-8499 PD 184352, Free Base, >99% O O [CI-1040] N H Size US$ ¤ £ ¥ F NH 5 mg 51 39 34 5,700 F Cl 10 mg 86 66 57 9,600 25 mg 159 123 105 17,800 50 mg 276 213 182 30,900 I 100 mg 415 321 274 46,400 P-9688 PD 325901, Free Base, >99% 200 mg 625 483 413 69,900 [MEK1/2 Inhibitor III] [PD0325901] 500 mg 1325 1024 876 148,100 1 g 1860 1438 1230 207,900 Size US$ ¤ £ ¥ NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 5 mg 44 34 29 4,900 10 mg 67 52 44 7,500 M.W. 478.66 C H ClF IN O [212631-79-3] 17 14 2 2 2 25 mg 159 146 125 21,100 Storage: Store at or below -20 ºC. Solubility: Soluble in 50 mg 258 199 171 28,800 DMSO at 50 mg/mL; soluble in ethanol at 8.3 mg/mL with 100 mg 398 308 263 44,500 slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 µM; 200 mg 519 401 343 58,000 buffers, serum, or other additives may increase or 500 mg 1180 912 780 131,900 decrease the aqueous solubility. Disposal: A 1 g 1995 1542 1319 223,000 NOTE: Euro, Pound and Yen prices are revised regularly. • PD184352 is an inhibitor of mitogen activated protein kinase Please visit www.LCLabs.com for our current prices. kinase (MEK or MAPKK). M.W. 482.19 c H F IN O [391210-10-9] • Antitumor activity of PD184352 is evident in preclinical 16 14 3 2 4 models, including pancreas, colon, and breast cancers, which are Storage: Store at or below -20 ºC. associated with its inhibition of pERK. Allen, L.F. et al., “CI-1040 Solubility: Soluble in DMSO at 12 mg/mL; soluble in (PD184352), a targeted signal transduction inhibitor of MEK ethanol at 6.3 mg/mL with slight warming; very poorly (MAPKK).” Semin. Oncol. 30: 105-116 (2003). soluble in water; maximum solubility in plain water is estimated to be about 50‑100 µM; buffers, serum, or other • PD184352 profoundly inhibited the growth of, and induced additives may increase or decrease the aqueous solubility. apoptosis in, ovarian tumor cells with mutations in either KRAS Disposal: A or BRAF. However, ovarian cancer cells containing wild-type sequences were not sensitive to PD184352. Pohl, G. et al., • PD 325901 is an inhibitor of mitogen activated protein kinase “Inactivation of the mitogen-activated protein kinase pathway kinase (MEK or MAPKK). The potency, solubility and as a potential target-based therapy in ovarian serous tumors with effectiveness of PD 325901 are greatly improved compared to KRAS or BRAF mutations.” Cancer Res. 65: 1994-2000 (2005). PD 184352 (CI-1040). Barrett, S.D. et al., “The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901.” • PD184352 inhibited C-Raf with an IC50 of 12 nM and inhibited more than 90% of ERK phosphorylation at a concentration of Bioorg. Med. Chem. Lett. 18: 6501-6504 (2008). 10 nM. In vivo, PD184352 decreased adenoma formation and • PD 325901 potently inhibited the growth of melanoma cells, with significantly restored lung structure. Kramer, B.W. et al., “Use of and without BRAF mutation. It also had an antiangiogenic activity. mitogenic cascade blockers for treatment of C-Raf induced lung Ciuffreda, L. et al., “Growth-inhibitory and antiangiogenic activity adenoma in vivo: CI-1040 strongly reduces growth and improves of the MEK inhibitor PD0325901 in malignant melanoma with or lung structure.” BMC Cancer 4: 24 (2004). without BRAF mutations.” Neoplasia 11: 720-731 (2009). • PD184352 inhibited the MAPK pathway and induced apoptosis • The sensitivity of RAS mutant cancers to MEK inhibitors depends through a pathway involved in dephosphorylation, aggregation on the activity of the phosphatidylinositol 3-kinase (PI3K) of Fas-associated death domain protein, and death receptor- pathway. Wee, S. et al., “PI3K pathway activation mediates

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 83 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

resistance to MEK inhibitors in KRAS mutant cancers.” Cancer Res. 69: 4286-4293 (2009). P-7177 Pemetrexed, Disodium Salt, Heptahydrate, >99% • The antiproliferative effect on cancer cells of PD 325901 can be [Alimta] [LY231514] [MTA] [Rolazar] [Tifolar] determined by a sensitive imaging biomarker, 3'-deoxy-3'-[18F] Size US$ ¤ £ ¥ fluorothymidine-positron emission tomography ([18F]FLT-PET). Leyton, J., “Noninvasive imaging of cell proliferation following 250 mg 57 43 37 5,500 mitogenic extracellular kinase inhibition by PD0325901.” 500 mg 81 61 52 7,800 Mol. Cancer Ther. 7: 3112-3121 (2008). 1 g 132 99 85 12,700 • PD 325901 potently inhibited the proliferation of thyroid cancer 2 g 224 168 144 21,600 cells with an IC50 of 0.06-0.78 µM. It also has synergistic 5 g 425 319 274 40,900 inhibitory effects when combined with phosphatidylinositol 10 g 570 427 368 54,900 3-kinase (PI3K) or NF-kB pathway inhibitors in most thyroid 25 g 1350 1012 871 129,900 cancer cell lines. Liu, D. and Xing, M., “Potent inhibition of NOTE: Euro, Pound and Yen prices are revised regularly. thyroid cancer cells by the MEK inhibitor PD0325901 and Please visit www.LCLabs.com for our current prices. its potentiation by suppression of the PI3K and NF-kappaB M.W. 597.48 C H N Na O •7H O pathways.” Thyroid 18: 853-864 (2008). 20 19 5 2 6 2 [357166-29-1] • Blockade of MEK/ERK signaling by PD 325901 greatly enhances the cytotoxicity induced by arsenic trioxide (ATO) through a Storage: Store at or below -20 °C. Solubility: Very caspase-dependent mechanism in human myeloma cell lines and in poorly soluble in DMSO; very poorly soluble in ethanol; tumor cells from patients with multiple myeloma. Lunghi, P. et al., soluble in water at 100 mg/mL; buffers, serum, or other “Targeting MEK/MAPK signal transduction module potentiates additives may increase or decrease the aqueous solubility. ATO-induced apoptosis in multiple myeloma cells through Disposal: A multiple signaling pathways.” Blood 112: 2450-2462 (2008). • Pemetrexed inhibits dihydrofolate reductase, thymidylate • A CAS number previously in use for this compound, 870474-62-7, synthase and glycinamide ribonucleotide formyltransferase with has been deleted by Chemical Abstracts Service. Ki values of 7 nM, 109 nM and 9.3 µM, respectively. Shih C. • We note that one of our competitors, Reagents Direct, et al., “LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate as of March 28, 2011, is claiming 99.7% purity for its that inhibits multiple folate-requiring enzymes.” Cancer Res. PD 325901, Free Base. This claim is not credible in general 57: 1116‑1123 (1997). chemical terms for this complex organic compound, nor in • Pemetrexed inhibits the proliferation of various human tumor terms of the sensitivity and reproducibility of generally utilized cell lines, including CCRF-CEM leukemia, GC3/C1 colon analytical techniques. carcinoma, and HCT-8 ileocecal carcinoma cells. Thymidine demonstrated its greatest protective effect at the IC of • Sold for laboratory or manufacturing purposes only; not for 50 human, medical, veterinary, food, or household use. pemetrexed. However, higher drug concentrations of pemetrexed required the combination of both thymidine plus hypoxanthine to • This product is offered for R&D use in accordance with (i) 35 protect the tumor cells. Shih C. et al., “LY231514, a pyrrolo[2,3-d] USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese pyrimidine-based antifolate that inhibits multiple folate-requiring Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent enzymes.” Cancer Res. 57: 1116-1123 (1997). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • The addition of folic acid supplementation with some antifolates and other common law exemptions of Canadian patent law; (vi) substantially diminished the host toxicity. However, natural Section 68B of the Patents Act of 1953 in New Zealand together folates inhibited the activity of pemetrexed by suppressing with the amendment of same by the Statutes Amendment Bill of folylpolyglutamate synthetase and thus decreasing the levels of 2002; (vii) such related legislation and/or case law as may be or active folylpolyglutamate pemetrexed congeners. Zhao R. et al., become applicable in the aforementioned countries; and (viii) such “Marked suppression of the activity of some, but not all, antifolate similar laws and rules as may apply in various other countries. compounds by augmentation of folate cofactor pools within tumor cells.” Biochem. Pharmacol. 61: 857-865 (2001). • Not available in some countries; not available to some institutions; not available for some uses. • The membrane transport system for pemetrexed includes reduced folate carrier (RFC), folate receptors, a folate transport carrier H with a low-pH optimum, and RFC-independent transport at neutral N O pH, etc. Chattopadhyay S. et al., “Pemetrexed: biochemical and HO O H F cellular pharmacology, mechanisms, and clinical applications.” OH N Mol. Cancer Ther. 6: 404-417 (2007). • Pemetrexed was approved in combination with cisplatin for F I the treatment of pleural mesothelioma in 2004. Hazarika M. ® F et al., “FDA drug approval summaries: pemetrexed (Alimta ).” Oncologist 9: 482-488 (2004). PD 406976 — see Gö 6976 (Cat. No. G-6203 on page 50). • Pemetrexed was also approved for the second-line treatment of PD-114720 — see Leptomycin B (Cat. No. L-6100 on page 63). locally advanced or metastatic non–small cell lung cancer in 2004. Cohen M.H. et al., “FDA drug approval summary: pemetrexed PD0325901 — see PD 325901, Free Base for injection (Alimta®) for the treatment of non-small cell lung (Cat. No. P-9688 on page 83). cancer.” Oncologist 10: 363-368 (2005). PD183805 — see Canertinib, Dihydrochloride Salt • Pemetrexed is the active ingredient in the drug sold under the (Cat. No. C-1201 on page 17). trade name Alimta®. The drug is currently approved in at least one country for use in patients with pleural mesothelioma as well as PDBu — see Phorbol 12,13-Dibutyrate (Cat. No. P-4833 on page 86). non-small cell lung cancer. NOTE: The pemetrexed product sold ® 4α-PDD — see 4α-Phorbol 12,13-Didecanoate by LC Laboratories is NOT Alimta and is NOT for human use. (Cat. No. P-2170 on page 86). • Our pemetrexed product is the disodium salt heptahydrate, whose CAS number is given above. The following CAS numbers PDGF Receptor Tyrosine Kinase Inhibitor IV — see JNJ-10198409, Free Base (Cat. No. J-4567 on page 59). correspond to other forms of pemetrexed: 137281-23-3 for the free acid; 150399-23-8 for the anhydrous disodium salt, and 357166- 30-4 for the disodium salt “hemipentahydrate” (2.5 H2O).

84 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• NOTE: Water content may vary from lot to lot. Please refer to the • Perifosine reduces Akt activity by inhibiting phosphorylation of elemental analysis provided in the Certificate of Analysis to obtain Akt at both Thr308 and Ser473. Kondapaka, S.B. et al., Perifosine, the water content for each lot. a novel alkylphospholipid, inhibits protein kinase B activation.” • Sold for laboratory or manufacturing purposes only; not for Mol. Cancer Ther. 2: 1093‑1103 (2003). human, medical, veterinary, food, or household use. • Perifosine inhibited the growth of breast, ovarian and prostate • This product is offered for R&D use in accordance with (i) 35 cancers by inducing apoptosis. Perifosine selectively blocks USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese AKT recruitment to the membrane and down-regulates the Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent phosphorylation of AKT and its downstream targets, particularly Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. S6, in various tumor cell lines and xenografts. Hennessy, B.T. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) et al., “Pharmacodynamic markers of perifosine efficacy.” and other common law exemptions of Canadian patent law; (vi) Clin. Cancer Res. 13: 7421‑7431 (2007). Section 68B of the Patents Act of 1953 in New Zealand together • Perifosine induces significant in vitro and in vivo cytotoxicity in with the amendment of same by the Statutes Amendment Bill of human multiple myeloma (MM), which is associated with down- 2002; (vii) such related legislation and/or case law as may be or regulation of Akt phosphorylation in tumor cells. c-Jun N-terminal become applicable in the aforementioned countries; and (viii) such kinase (JNK) plays a critical role in perifosine-induced apoptosis. similar laws and rules as may apply in various other countries. Perifosine enhances dexamethasone, doxorubicin, melphalan and • Not available in some countries; not available to some institutions; bortezomib-induced MM cell cytotoxicity. Hideshima, T. et al., not available for some uses. “Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple O Na+ myeloma cells.” Blood 107: 4053‑4062 (2006). O • No significant clinical activity of perifosine against androgen independent prostate cancer was observed in + a phase II study. Posadas, E.M. et al., “A phase II study H O O Na H of perifosine in androgen independent prostate cancer.” H2N N N N O Cancer Biol. Ther. 4: 1133‑1137 (2005). H N • Twenty-three patients with advanced soft tissue sarcoma received 66 cycles of treatment with perifosine (1 cycle = O 4 weeks). The 3 and 6 month progression-free survival was 22% and 9%. Bailey, H.H. et al., “Phase II study of daily oral PEP005 — see Ingenol 3-Angelate (Cat. No. I-5900 on page 55). perifosine in patients with advanced soft tissue sarcoma.” P-6522 Perifosine, >99% Cancer 107: 2462‑2467 (2006). P-7177 2010-04-03-tdr-CD-rev.eps • In chemical structure terms, perifosine is known as a “betaine” or Synonyms: [KRX-0401] [NKA17] “zwitterion,” which can also be referred to as an “internal salt.” These terms are applied to compounds that have a net neutral Size US$ ¤ £ ¥ charge for the entire molecule but which contain both a positively- 5 mg 63 49 42 7,000 charged functional group (such as a quaternary ammonium cation 10 mg 99 77 65 11,100 in the case of perifosine) and a negatively charged functional 25 mg 178 138 118 19,900 group, such as a phosphate or carboxylate anion. 50 mg 275 213 182 30,700 • Sold for laboratory or manufacturing purposes only; not for 100 mg 444 343 294 49,600 human, veterinary, food, or household use. 200 mg 716 553 473 80,000 • This product is offered for R&D use in accordance with (i) 35 500 mg 1130 873 747 126,300 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 1 g 1622 1254 1072 181,300 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent NOTE: Euro, Pound and Yen prices are revised regularly. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Please visit www.LCLabs.com for our current prices. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) M.W. 461.66 c25H52NO4P [157716-52-4] M.I. 14: 7165 Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of Storage: Store at or below -20 ºC. Solubility: Very poorly 2002; (vii) such related legislation and/or case law as may be or soluble in DMSO; soluble in ethanol at 200 mg/mL; soluble become applicable in the aforementioned countries; and (viii) such in water at 50 mg/mL with warming; buffers, serum, or similar laws and rules as may apply in various other countries. other additives may increase or decrease the aqueous • Not available in some countries; not available to some institutions; solubility. Disposal: A not available for some uses. • Perifosine, also known as KRX-0401, is a novel synthetic CH alkylphospholipid and is a new kind of antitumor agent which 3 O N CH targets cell membranes and blocks Akt activation. + 3 P • The structure of perifosine is similar to naturally-occurring H C O O phospholipids. Perifosine (5 µM) inhibited the growth of PC-3 3 O _ prostate carcinoma cells by 50% in 24 hr and induced cell death PF-02341066 — see Crizotinib, Free Base in virtually all cells by 48 hr. Kondapaka, S.B. et al., “Perifosine, (Cat. No. C-7900 on page 23). a novel alkylphospholipid, inhibits protein kinase B activation.” Mol. Cancer Ther. 2: 1093‑1103 (2003). PF-1066 — see Crizotinib, Free Base (Cat. No. C-7900 on page 23).

• Perifosine inhibits the growth of variant cells, with GI50 values PF-2341066 — see Crizotinib, Free Base of 1-10 µM for K-562, SUDHL-7, HL-60, PC-3, Colo-205, and (Cat. No. C-7900 on page 23). MESA-SA (CRL-1976) cells, 11-30 µM for MG-63 (CRL-1427), H-3386, RD (CCL-136), HT-29, MDA-435, SW-620, CCRF-7, PHA-290940AD – see Sunitinib, Malate Salt (Cat. No. S-8803 on H-1355, SAJA-1 (CRL-2098), and DU-145 cells, and >30 µM page 110) and Sunitinib, Free Base (Cat. No. S-8877 on page 109). for MCF-7, Hos (CRL-1543), and LnCAP cells. Kondapaka, S.B. Pharmorubicin — see Epirubicin, Hydrochloride Salt et al., “Perifosine, a novel alkylphospholipid, inhibits protein (Cat. No. E-8000 on page 35). kinase B activation.” Mol. Cancer Ther. 2: 1093‑1103 (2003).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 85 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

P-1010 Phorbol, >99% P-2170 4α-Phorbol 12,13-Didecanoate, >99% [4α-PDD] Size US$ ¤ £ ¥ 1 mg 56 41 35 4,600 Size US$ ¤ £ ¥ 5 mg 195 144 121 16,000 1 mg 68 50 42 5,600 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 5 mg 195 144 121 16,000 10 mg 325 239 202 26,700 M.W. 364.43 c20H28O6 [17673-25-5] 25 mg 640 471 397 52,600 M.I. 14: 7332 NOTE: Euro, Pound and Yen prices are revised regularly. Storage: Store at or below -20 °C. Solubility: Soluble in Please visit www.LCLabs.com for our current prices. ethanol, DMSO or water. Disposal: A M.W. 672.93 C40H64O8 [27536-56-7] • Unsubstituted parent diterpene from which phorbol esters are Storage: Store at or below -20 °C. Solubility: Soluble in derived; biologically inactive in most assays. DMSO or ethanol. Disposal: A • Please request Technical Note #30 for a note on nomenclature. • Negative control for studies with Phorbol 12,13-Didecanoate, • Sold for laboratory or manufacturing purposes only; not for for example, see Trewyn, R.W. and Gatz, H.B., “Altered human, medical, veterinary, food, or household use. growth properties of normal human cells induced by phorbol 12,13-didecanoate.” In Vitro 20: 409‑15 (1984). HO OH • Please request Technical Note #13 for additional information. • 4α-PDD Activation of TRPV4 Channels Long thought to be H H a biologically inactive or extremely weak phorbol ester analog H (i.e., an ED >25 µM for binding to protein kinase C compared OH 50 to ~1 nM potency for PMA), 4α-PDD has now been shown to be O OH a reasonably potent activator of two TRPV4 channels, namely OH human VRL-2 and murine TRP12 channels [H. Watanabe et al., J. Biol. Chem. 277: 13569-13577 (2002)]. The ED50 of 4α-PDD P-4833 Phorbol 12,13-Dibutyrate, >99% for activation of the TRP12 channel was ~400 nM, and ~185 nM [PDBu] for increasing internal calcium levels in 1321N1 astrocytoma cells expressing human VRL-2. This work extends earlier results Size US$ ¤ £ ¥ showing non-phorbol-ester-like effects of 4α-PDD [H. Reeve et al., Pflugers Arch. Eur. J. Physiol. 429: 729-737 (1995)] and 1 mg 39 30 24 3,300 4α-phorbol 12,13-dibutyrate (4α-PDBu) [D. Doerner et al., 5 mg 121 92 75 10,100 J. Neurosci. 10: 1699-1706 (1990)] on calcium currents. 10 mg 215 163 133 18,000 Because 4α-PDD has few, if any, recognized biological NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. effects at sub-micromolar concentrations other than these effects on TRPV4 channels, Watanabe et al. certainly seem justified in M.W. 504.61 c28H40O8 [37558-16-0] stating that “4α-PDD can be used as a robust and reliable tool to WARNING: Highly irritant to skin and mucous membranes. study several features of TRPV channels and to probe functional SPECIAL HAZARD: TUMOR PROMOTER. Gloves and effects of the activation of this channel in in vivo systems”. mask should be worn when using this compound. Care That said, it is also important to note that absolute selectivity of must be taken to prevent contact through all routes of 4α-PDD for activating TRPV4 channels may not yet have been exposure. thoroughly tested. Though 4α-PDD has been shown over the Storage: Store at or below -20 °C. Solubility: Soluble in years to have little or no effect in a fairly wide range of biological DMSO or ethanol. Disposal: A assays, it might prove to have other, as-yet-unidentified activities if subjected to more extensive testing against various targets. • Widely used PKC activator; less potent than PMA, but also less [As an aside, we point out that reference #25 in the Watanabe hydrophobic, making it easier to wash out of cells in tissue culture. article, cited in support of the inactivity of 4α-PDD on PKC, • This was the ligand used, in radioactive form, in the discovery appears not to contain any mention at all of 4α-PDD or other of the phorbol ester receptor. Driedger, P.E. and Blumberg, P.M. 4α-phorbol esters.] Proc. Natl. Acad. Sci. USA 77: 567-571 (1980). [Also, see below for an important note about nomenclature. 3 • Tritium-labeled PDBu, [ H]PDBu, is available from several Technically, 4α-PDD is not a phorbol ester, it is a 4α-phorbol suppliers of radiochemicals. ester — a small but important distinction — and must always • Please request Technical Note #14 for additional information. be specified as such to avoid confusion with the dramatically • Sold for laboratory or manufacturing purposes only; not for different properties of the phorbol esters.] human, medical, veterinary, food, or household use. Surprisingly (in view of historical structure-activity data), PMA (phorbol 12-myristate 13-acetate), the classical nanomolar-potency C H 3 7 O PKC activator, was shown by Watanabe et al. to be 10- to 50-fold O weaker than 4α-PDD for activation of the TRPV4 channels. If O O C H 3 7 both PMA and 4α-PDD were targeting a PKC-related protein, H C 3 via a mechanism fundamentally similar to that of classical PKC H H activation by phorbol esters, PMA would be expected to be many H OH orders of magnitude more potent than 4α-PDD. Watanabe et al. tested a wide range of PMA and 4α-PDD concentrations, and O OH there appears to be no doubt that the relative potencies expected OH for PMA and 4α-PDD for classical PKC-related effects are strikingly reversed for the TRPV4 channel activation phenomenon. Furthermore, in some assays PMA was merely a “partial agonist”, showing only 50-65% of the response elicited by 4α-PDD. The PMA/4α-PDD potency inversion in turn strongly suggests that 4α-PDD must be acting via a mechanism distinct from the classical interaction of a phorbol 12,13-diester with a phorbol

86 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

ester/diacylglycerol-type receptor target, such as those found on the PKC family of proteins. Given the long history and, until now, P-1680 Phorbol 12-Myristate 13-Acetate, >99.5% largely settled picture of the biological properties of phorbol and [Cocarcinogen A1] [PMA] 4α-phorbol esters, this question of mechanism is of high interest, [12-O-Tetradecanoyphorbol 13-Acetate] [TPA] and the answer(s) might turn out to have a wide impact on several areas of pharmacology. Size US$ ¤ £ ¥ LC Laboratories also offers other 4α-phorbol diesters of varying 1 mg 15 11 9 1,300 hydrophobicity; these presumably can be used for structure- 5 mg 69 52 43 5,800 activity studies of the TRPV4 activation effect. For example, 10 mg 124 94 77 10,400 we offer 4α-PMA (Cat. No. P-8880 on page 87) which is less 25 mg 265 201 164 22,100 hydrophobic than 4α-PDD. 100 mg 995 756 615 83,100 Analogs of 4α-PDD have considerable potential utility. The NOTE: Euro, Pound and Yen prices are revised regularly. high hydrophobicity (high lipid partition coefficient) of 4α-PDD Please visit www.LCLabs.com for our current prices. makes it quite soluble in cellular membrane compartments, and M.W. 616.83 c36H56O8 [16561-29-8] it is reliably presumed to be difficult to wash this compound out M.I. 14: 7332 of membrane preparations or cell cultures. 4α-PMA or 4α-PDBu may prove to be less potent than 4α-PDD, but if they retain WARNING: Highly irritant to skin and mucous membranes. sufficient potency vis-a-vis 4α-PDD, they might be preferable as SPECIAL HAZARD: TUMOR PROMOTER. Gloves and research tools because of their enhanced potential to equilibrate mask should be worn when using this compound. Care among aqueous and lipid cellular compartments and to be washed must be taken to prevent contact through all routes of out of experimental preparations. exposure. In the past, in addition to 4α-PMA, we have also made some Storage: Store at or below -20 °C. Solubility: Soluble in other 4α-phorbol diesters, such as 4α−PDBu and 4α-phorbol DMSO or ethanol. Disposal: A 12,13-diacetate, a compound of very low hydrophobicity. These • This is the most commonly used phorbol ester. It binds to and other 4α-phorbol derivatives are not currently listed as LC Labs™ activates protein kinase C, causes an extremely wide range of products but are available by special request. We are also pleased effects in cells and tissues, and is a very potent mouse skin tumor to offer all of our 4α-phorbol products in bulk quantities at promoter. Blumberg, P.M. CRC Crit. Rev. Toxicol. 8: 153-197 and substantial discounts. 199-234 (1980). • Chemical Structures. The primary structural difference between • Although PMA is quite toxic, it has shown anti-leukemic 4α-PDD and the highly potent phorbol ester-type PKC activators and anti-neutopenic activity in humans. Han, Z.T. et al. is the configuration at C4. In the highly active phorbol ester Proc. Natl. Acad. Sci. USA 95: 5357‑5361 (1998) and family, the hydroxy group at C4 is in the β configuration, i.e., Proc. Natl. Acad. Sci. USA 95: 5362‑5365 (1998). rising up out of the two-dimensional structure as viewed on paper • Beginning with our lot #F-151, we now guarantee purity of 99.5% or a computer monitor. The 4 -phorbol esters such as 4 -PDD, α α or greater for this product as measured by HPLC at 254nm. 4α-PMA and 4α-PDBu have the 4-OH group oriented down below the paper or computer screen’s two-dimensional plane. • Please request Technical Note #14 for additional information. • Nomenclature. Unless “4α” is specified, all “phorbol” compounds • Sold for laboratory or manufacturing purposes only; not for are automatically defined, by operation of standard chemical human, medical, veterinary, food, or household use.

nomenclature conventions, as having the 4β-configuration, as part C H of the meaning of the word “phorbol”. This is much like the word 13 27 O O “cholesterol”, which automatically means that its hydroxy group O O at carbon 3 is in the β configuration; there is no need to specify H3C “3β-cholesterol”, whereas a cholesterol derivative with a 3α H hydroxy group would require a “3α-cholesterol” specification. H H To avoid confusion in this field, it is useful to note that, OH technically, 4α-PDD is not a “phorbol ester”, it is a “4α-phorbol O OH ester”, and the structural differences, though minor overall, are OH quite significant biologically. Given the extreme differences in their biological properties, both on PKC and TRPV4 channel- P-8880 4α-Phorbol 12-Myristate 13-Acetate, >99% based phenomena, efforts to maintain distinctive names for members of these two biologically quite distinct classes of [4α-PMA] [4α-12-O-Tetradecanoylphorbol 13-Acetate] compounds appear to be well justified. [4α-TPA] • Sold for laboratory or manufacturing purposes only; not for Size US$ ¤ £ ¥ human, medical, veterinary, food, or household use. 1 mg 59 45 36 4,900 C H 9 19 O 5 mg 239 182 148 20,000

O O 10 mg 382 290 236 31,900 O C9H19 NOTE: Euro, Pound and Yen prices are revised regularly. H3C Please visit www.LCLabs.com for our current prices. H H M.W. 616.83 c36H56O8 [63597-44-4] H OH Storage: Store at or below -20 °C. Solubility: Soluble in DMSO or ethanol. Disposal: A O OH OH • Negative control for studies with PMA (Cat. No. P-1680 on page 87). Van Duuren, B.L. et al. Cancer Res. 39: 2644‑2646 (1979). • Please request Technical Note #13 for additional information. • 4α-Phorbol Ester Activation of TRPV4 Channels Though long thought to be a biologically inactive or extremely weak phorbol ester analog (i.e., an ED50 >25 µM for binding to protein kinase C), 4α-PMA may prove to be a reasonably potent activator of TRPV4 channels, with utility for structure-activity studies of this phenomenon. The supposition of agonist activity for 4α-PMA on

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 87 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

TRPV4 channels is based on the potent agonist response elicited • This research compound is the free base form of PI-103. We by the very similar compound, 4α-PDD, in systems containing also offer the HCl salt form (see PI-103, Hydrochloride Salt, human VRL-2 and murine TRP12 channels [H. Watanabe et al., Cat. No. P-9088 on page 89). J. Biol. Chem. 277: 13569-13577 (2002)]. See the entry for • PI-103 is a potent and selective PI3K inhibitor with low IC50 4α-PDD (Cat. No. P-2170 on page 86) for a more extensive values against PI3K isoforms p110α (2 nM), p110β (3 nM), description. p110δ (3 nM), and p110γ (15 nM). PI-103 at 0.5 µM also • Sold for laboratory or manufacturing purposes only; not for inhibited TORC1 by 84% and demonstrated an IC50 of 14 nM human, medical, veterinary, food, or household use. against DNA-PK. PI-103 potently inhibited proliferation and • Chemical Structures. The primary structural difference between invasion of a wide variety of human cancer cells in vitro and 4α-PDD and the highly potent phorbol ester-type PKC activators induced tumor growth delay in eight different human cancer is the configuration at C4. In the highly active phorbol ester xenograft models. PI-103 also demonstrated antiangiogenic family, the hydroxy group at C4 is in the β configuration, i.e., potential. Raynaud, F.I. et al., "Pharmacologic characterization rising up out of the two-dimensional structure as viewed on paper of a potent inhibitor of class I phosphatidylinositide 3-kinases." or a computer monitor. The 4α-phorbol esters such as 4α-PDD, Cancer Res. 67: 5840‑5850 (2007). 4α-PMA and 4α-PDBu have the 4-OH group oriented down below • PI-103 had antitumor activity in two gefitinib-resistant (see the paper or computer screen’s two-dimensional plane. Gefitinib, Free Base, Cat. No. G-4408 on page 45) non-small cell • Nomenclature. Unless “4α” is specified, all “phorbol” compounds lung cancer cell lines, A549 and H460, possibly by simultaneously are automatically defined, by operation of standard chemical inhibiting p70s6k phosporylation and Akt phosphorylation due nomenclature conventions, as having the 4β-configuration, as part to mTOR inhibition. Zou, Z.Q. et al., "A novel dual PI3Kalpha/ of the meaning of the word “phorbol”. This is much like the word mTOR inhibitor PI-103 with high antitumor activity in non-small “cholesterol”, which automatically means that its hydroxy group cell lung cancer cells." Int. J. Mol. Med. 24: 97‑101 (2009). at carbon 3 is in the β configuration; there is no need to specify • PI-103 was mainly cytostatic for human leukemic cell lines and “3β-cholesterol”, whereas a cholesterol derivative with a 3α induced cell cycle arrest in the G1 phase. In blast cells from hydroxy group would require a “3α-cholesterol” specification. AML patients, PI-103 inhibited leukemic proliferation and the To avoid confusion in this field, it is useful to note that, clonogenicity of leukemic progenitors, and induced mitochondrial technically, 4α-PDD is not a “phorbol ester”, it is a “4α-phorbol apoptosis. Park, S. et al., "PI-103, a dual inhibitor of Class IA ester”, and the structural differences, though minor overall, are phosphatidylinositide 3-kinase and mTOR, has antileukemic quite significant biologically. Given the extreme differences in activity in AML." Leukemia 22: 1698‑1706 (2008). their biological properties, both on PKC and TRPV4 channel- • PI-103 inhibited the proliferation of glioma cells, possibly by based phenomena, efforts to maintain distinctive names for its ability to inhibit both PI3 kinaseα and mTOR. It showed members of these two biologically quite distinct classes of significant inhibitory activity in xenografted tumors with compounds appear to be well justified. no observable toxicity. Fan, Q.W. et al., "A dual PI3 kinase/ mTOR inhibitor reveals emergent efficacy in glioma." C H 13 27 O Cancer Cell 9: 341‑349 (2006). O O O • A combined treatment with arsenic disulfide and PI-103 synergistically killed non-acute promyelocytic leukemia cells and H3C H promoted their differentiation in vitro. Hong, Z. et al., "Arsenic H disulfide synergizes with the phosphoinositide 3-kinase inhibitor H OH PI-103 to eradicate acute myeloid leukemia stem cells by inducing differentiation." Carcinogenesis 32: 1550‑1558 (2011). O OH OH • PI-103 inhibited endothelial cell proliferation and survival in vitro and tumor growth in vivo possibly by blocking activation P-9099 PI-103, Free Base, >99% of both PI3K and mTOR in vGPCR-expressing endothelial cells. Chaisuparat, R. et al., "Dual inhibition of PI3Kα and Synonyms: [PI3-Kinase α Inhibitor 1] [PIK-103] mTOR as an alternative treatment for Kaposi's sarcoma." Cancer Res. 68: 8361‑8368 (2008). Size US$ ¤ £ ¥ • This PI-103 product is the free base form, whose CAS number is 5 mg 38 28 22 4,600 given above. The CAS number of the hydrochloride salt form is New! 10 mg 52 38 31 6,300 371935-79-4. 25 mg 117 86 69 14,100 • Sold for laboratory or manufacturing purposes only; not for 50 mg 199 146 117 24,000 human, veterinary, food, or household use. 100 mg 358 263 210 43,200 • This product is offered for R&D use in accordance with (i) 35 200 mg 614 451 361 74,200 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 250 mg 739 543 434 89,300 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 500 mg 1290 949 758 155,800 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. NOTE: Euro, Pound and Yen prices are revised regularly. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Please visit www.LCLabs.com for our current prices. and other common law exemptions of Canadian patent law; (vi) M.W. 348.36 c H N O [371935-74-9] Section 68B of the Patents Act of 1953 in New Zealand together 19 16 4 3 with the amendment of same by the Statutes Amendment Bill of Storage: Store at or below -20 ºC. Solubility: Soluble in 2002; (vii) such related legislation and/or case law as may be or DMSO at 40 mg/mL; very poorly soluble in ethanol; very become applicable in the aforementioned countries; and (viii) such poorly soluble in water; maximum solubility in plain water similar laws and rules as may apply in various other countries. is estimated to be about 5-10 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. • Not available in some countries; not available to some institutions; Disposal: A not available for some uses. • PI-103 is a dual inhibitor of class IA phosphatidylinositide O 3-kinase (PI3K) and mTOR. PI3K is a class of lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) to N

generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 O activates Akt and mTOR, and plays important roles in cell growth N OH N and survival. N

88 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

P-9088 PI-103, Hydrochloride Salt, >99% P-7858 PIK-75, Free Base, >99% Synonyms: [PI3-Kinase α Inhibitor 1] [PIK-103 HCl] Synonyms: [PI3-Kinase α Inhibitor VIII]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 5 mg 38 28 22 4,600 10 mg 22 16 14 1,700 New! 10 mg 52 38 31 6,300 25 mg 42 31 27 3,300 25 mg 117 86 69 14,100 50 mg 75 56 48 5,800 50 mg 199 146 117 24,000 100 mg 128 96 82 9,900 100 mg 358 263 210 43,200 200 mg 249 186 159 19,300 200 mg 614 451 361 74,200 1 g 1155 862 737 89,700 250 mg 739 543 434 89,300 NOTE: Euro, Pound and Yen prices are revised regularly. 500 mg 1290 949 758 155,800 Please visit www.LCLabs.com for our current prices. NOTE: Euro, Pound and Yen prices are revised regularly. M.W. 452.28 c16H14BrN5O4S [372196-67-3] Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 ºC. Solubility: Soluble in M.W. 384.82 c19H16N4O3•HCl [371935-79-4] DMSO. Disposal: A Storage: Store at or below -20 ºC. Solubility: Soluble in • This is the free base form of PIK-75; please see the other form of DMSO. Disposal: A this product, PIK-75, Hydrochloride Salt (Cat. No. P-7050 on page • This research compound is the hydrochloride salt form of 89), for further technical information. PI‑103; see the free base form of this product (PI‑103, Free Base, • This PIK-75 product is the free base, whose CAS number is given Cat. No. P-9099 on page 88) for further technical information about above. The CAS number of the hydrochloride salt is 372196-77-5. both of these research compounds. • Sold for laboratory or manufacturing purposes only; not for • This PI-103 product is the hydrochloride salt, whose CAS human, medical, veterinary, food, or household use. number is given above. The CAS number of the free base form is • This product is offered for R&D use in accordance with (i) 35 371935‑74‑9. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Sold for laboratory or manufacturing purposes only; not for Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent human, veterinary, food, or household use. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • This product is offered for R&D use in accordance with (i) 35 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese and other common law exemptions of Canadian patent law; (vi) Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Section 68B of the Patents Act of 1953 in New Zealand together Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. with the amendment of same by the Statutes Amendment Bill of Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 2002; (vii) such related legislation and/or case law as may be or and other common law exemptions of Canadian patent law; (vi) become applicable in the aforementioned countries; and (viii) such Section 68B of the Patents Act of 1953 in New Zealand together similar laws and rules as may apply in various other countries. with the amendment of same by the Statutes Amendment Bill of • Not available in some countries; not available to some institutions; 2002; (vii) such related legislation and/or case law as may be or not available for some uses. become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. N • Not available in some countries; not available to some institutions; N not available for some uses. Br N O O O N S H C CH 3 3 . N HCl

O N OH O N N O N P-7050 PIK-75, Hydrochloride Salt, >99% PI3-Kinase a Inhibitor 1 — see PI-103, Free Base [PI3-Kinase a Inhibitor VIII] (Cat. No. P-9099 on page 88) and PI-103, Hydrochloride Salt (Cat. No. P-9088 on page 89). Size US$ ¤ £ ¥ PI3-Kinase a Inhibitor VIII — see PIK-75, Free Base 10 mg 22 16 14 1,700 (Cat. No. P-7858 on page 89) and PIK-75, Hydrochloride Salt 25 mg 42 31 27 3,300 (Cat. No. P-7050 on page 89). 50 mg 75 56 48 5,800 Picato — see its active ingredient, namely Ingenol 3-Angelate 100 mg 128 96 82 9,900 (Cat. No. I-5900 on page 55). 200 mg 249 186 159 19,300 Pictilisib — see GDC-0941, Free Base (Cat. No. G-9252 on page 44). 1 g 1155 862 737 89,700 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices.

M.W. 488.74 C16H14BrN5O4S•HCl [372196-77-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A • PIK-75 is a preferential inhibitor of the p110a/g forms of phosphatidylinositol 3-kinase (PI3K), which comprise a class of lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 activates Akt and mTOR, and plays important roles in cell growth and survival.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 89 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• PIK-75-mediated anti-inflammatory effects are associated with • PIK-90 is a synthetic phosphoinositide 3-kinase (PI3K) inhibitor. dramatic inhibition of AKT phosphorylation, IKK activation The p110a isoform of PI3K is the primary insulin-responsive and NF‑kB transcription. Dagia, N.M. et al., “A Preferential PI3K in cultured cells. Compounds targeting p110a block the p110a/g PI3K Inhibitor Attenuates Experimental Inflammation acute effects of insulin treatment in vivo. A p110b inhibitor has no by Suppressing the Production of Proinflammatory Mediators effect on insulin treatment. Zachary, A. et al., “A Pharmacological in NF‑kB Dependent Manner.” Am. J. Physiol. Cell Physiol. Map of the PI3-K Family Defines a Role for p110a in Insulin 298: C929‑C941 (2010). Signaling.” Cell 125: 733-747 (2006).

• PIK-75 completely inhibited adipocyte differentiation. Kim, J.E. • PIK-90 is a class I p110a inhibitor (IC50 = 11 nM). It also blocks et al., “Investigating the role of class-IA PI 3-kinase isoforms in p110g (IC50 = 18 nM), and to a lesser extent p110d (IC50 = 58 nM) adipocyte differentiation.” Biochem. Biophys. Res. Commun. and p110b (IC50 = 350 nM). Niedermeier, M. et al., “Isoform- 379: 830-834 (2009). selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 • Insulin-like growth factor-1 (IGF-1) potentiates PAR-1-mediated signaling and overcome stromal cell-mediated drug resistance in platelet aggregation. PIK-75 and PI-103 completely inhibited this chronic lymphocytic leukemia: a novel therapeutic approach.” potentiation, indicating PI3Ka; is essential for the enhancement by Blood 113: 5549-5557 (2009). IGF-1 of platelet responses. Hers, I., “Insulin-like growth factor-1 • PIK-90, PI-103, or IC87114 inactivated PI3K and led to potentiates platelet activation via the IRS/PI3Kalpha pathway.” uncontrolled sequential switching from IgG1 to IgE. Zhang, Blood 110: 4243-4252 (2007). T.T. et al., “Genetic or pharmaceutical blockade of p110d • In addition to the p110a isotype of PI3K , p110b and p110d phosphoinositide 3-kinase enhances IgE production.” can also play a role in insulin signalling. Chaussade, C. et al., J. Allergy Clin. Immunol. 122: 811-819 (2008). “Evidence for functional redundancy of class IA PI3K isoforms in • PIK-90 induced the proliferative arrest of a panel of glioma cell insulin signalling.” Biochem. J. 404: 449-458 (2007). lines. Combining PIK-90 and the mTORC1 inhibitor rapamycin • Our PIK-75 product, whose CAS number appears above, is induced a profound cell cycle arrest, which is similiar to PI- the hydrochloride salt. The CAS number for the free base is 103 treatment alone. Fan, Q. et al., “A dual PI3 kinase/mTOR 372196‑67‑3. inhibitor reveals emergent efficacy in glioma.” Cancer Cell 9: 341‑349 (2006). • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • PI3K inhibitors (PIK-90 and PI-103) enhanced the cytotoxic effects of radiation in PTEN wild type and mutant glioma cells. • This product is offered for R&D use in accordance with (i) 35 Chen, J.S. et al., “Characterization of structurally distinct, isoform- USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese selective phosphoinositide 3'-kinase inhibitors in combination with Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent radiation in the treatment of glioblastoma.” Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Mol. Cancer Ther. 7: 841-850 (2008). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) • Our PIK-90 product, whose CAS number appears above, is the Section 68B of the Patents Act of 1953 in New Zealand together free base. The CAS number of the hydrochloride salt is with the amendment of same by the Statutes Amendment Bill of 677338-13-5. 2002; (vii) such related legislation and/or case law as may be or • Other CAS numbers previously assigned to PIK-90, namely become applicable in the aforementioned countries; and (viii) such 1029940-40-6 and 1206911-27-4, have been deleted by CAS and similar laws and rules as may apply in various other countries. are no longer in use. • Not available in some countries; not available to some institutions; • Sold for laboratory or manufacturing purposes only; not for not available for some uses. human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 N USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese . HCl N Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Br N O Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. S O CH Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) N 3 H C and other common law exemptions of Canadian patent law; (vi) 3 Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or NO 2 become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; P-9050 PIK-90, Free Base, >99% not available for some uses.

Size US$ ¤ £ ¥ OMe 5 mg 44 34 29 4,900 N 10 mg 62 48 41 6,900 OMe 25 mg 139 107 92 15,500 N N 50 mg 258 199 171 28,800 N N 100 mg 475 367 314 53,100 H

200 mg 855 661 565 95,600 O NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. PIK-103 — see PI-103, Free Base (Cat. No. P-9099 on page 88).

M.W. 351.36 c18H17N5O3 [677338-12-4] PIK-103 HCl — see PI-103, Hydrochloride Salt Storage: Store at or below -20 ºC. Solubility: Soluble in (Cat. No. P‑9088 on page 89). DMSO at 0.5 mg/mL with warming; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water is estimated to be about 20-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

90 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

Cl P-6040 Pimecrolimus, >99% H [Elidel] [SDZ-ASM-981] H CO CH 3 3 H C O Size US$ ¤ £ ¥ 3

25 mg 55 43 36 6,100 H O OH 50 mg 82 63 54 9,200 N O 100 mg 148 114 98 16,500 O CH O 3 200 mg 258 199 171 28,800 OH H C CH 300 mg 336 260 222 37,600 3 O 3 1 g 975 754 645 109,000 NOTE: Euro, Pound and Yen prices are revised regularly. OCH OCH Please visit www.LCLabs.com for our current prices. 3 3 M.W. 810.45 c H ClNO [137071-32-0] 43 68 11 P-7600 PKC412, >99% M.I. 14: 7429 [4'-N-Benzoyl Staurosporine] [CGP 41251] Storage: Store at or below -20 °C. Solubility: Soluble in [Midostaurin] DMSO and ethanol, up to about 25 mg/mL. Disposal: A • Pimecrolimus, a rapamycin (sirolimus) derivative, is a cell- Size US$ ¤ £ ¥ selective inhibitor of inflammatory cytokines specifically 1 mg 51 38 32 4,500 developed for the treatment of inflammatory skin diseases, such 5 mg 135 101 84 12,000 as atopic dermatitis, allergic contact dermatitis, irritant contact 10 mg 218 163 135 19,400 dermatitis, and plaque-type psoriasis. It inhibits the production 25 mg 425 318 263 37,900 of inflammatory cytokines in T cells and mast cells and prevents the release of preformed inflammatory mediators from mast 50 mg 588 441 364 52,400 cells. Stuetz A. et al., “Pimecrolimus (Elidel, SDZ ASM 981)— 100 mg 1048 785 650 93,500 preclinical pharmacologic profile and skin selectivity.” 200 mg 1775 1330 1100 158,300 Semin. Cutan. Med. Surg. 20: 233-241 (2001). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. • In 13 of 26 (50%) lesions of vitiligo, repigmentation was noted after a 6 month treatment of 1% pimecrolimus with a median M.W. 570.64 C35H30N4O4 [120685-11-2] percentage of repigmentation of 72.9% (interquartile range: M.I. 14: 6185 30.5-98.3%). Duration of vitiligo and total affected body surface Storage: Store at or below -20 ºC. Solubility: Soluble in area tended to be inversely correlated with the success rate of DMSO at 100 mg/mL; soluble in ethanol at 5 mg/mL with treatment. Boone B. et al., “Topical pimecrolimus in the treatment warming; very poorly soluble in water; maximum solubility of vitiligo.” Eur. J. Dermatol. 17: 55-61 (2007). in plain water is estimated to be about 10-20 µM; buffers, • Pimecrolimus is active against mild to moderate atopic dermatitis serum, or other additives may increase or decrease the in adults and children aged ≥ 2 years. Pimecrolimus improved the aqueous solubility. Disposal: A signs and symptoms of atopic dermatitis and delayed time to a • The staurosporine analog, PKC412, inhibits a variety of serine/ major flare. Hebert A.A., “Review of pimecrolimus cream 1% for threonine and tyrosine kinases including PKC (IC 50 nM), cyclic the treatment of mild to moderate atopic dermatitis.” 50 AMP-dependent protein kinase (IC50 2.4 µM), S6 kinase (IC50 Clin. Ther. 28: 1972-1982 (2006). 5.0 µM), and EGFR (epidermal growth factor receptor) tyrosine- • Pimecrolimus is the active ingredient in the drug sold under the kinase activity (IC50 3.0 µM). Meyer, T. et al., “A derivative of trade name Elidel®. This drug is an immunomodulating agent staurosporine (CGP 41 251) shows selectivity for protein kinase used in the treatment of atopic dermatitis (eczema). NOTE: the C inhibition and in vitro anti-proliferative as well as in vivo anti- pimecrolimus sold by LC Laboratories is NOT Elidel® and is NOT tumor activity.” Int. J. Cancer 43: 851-856 (1989). for human use. • PKC412 inhibits autophosphorylation of platelet-derived growth • Sold for laboratory or manufacturing purposes only; not for factor (PDGF) receptor in BALB/c 3T3 cells at submicromolar human, medical, veterinary, food, or household use. concentrations. Andrejauskas-Buchdunger, E. and Regenass, U., • This product is offered for R&D use in accordance with (i) 35 “Differential inhibition of the epidermal growth factor-, platelet- USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese derived growth factor-, and protein kinase C-mediated signal Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent transduction pathways by the staurosporine derivative CGP Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 41251.” Cancer Research, 52: 5353-5358 (1992). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • PKC412 strongly blocks the proliferation of ras-transformed and other common law exemptions of Canadian patent law; (vi) pancreatic cancer cells (TUC-3) by causing apoptosis and Section 68B of the Patents Act of 1953 in New Zealand together induction of phenotypic reversion. Way, D. et al., “A protein with the amendment of same by the Statutes Amendment Bill of kinase C inhibitor induces phenotypic reversion of ras-transformed 2002; (vii) such related legislation and/or case law as may be or pancreatic cancer cells and cooperatively blocks tumor cell become applicable in the aforementioned countries; and (viii) such proliferation with an anti- ras peptide.” Cancer Chemother. similar laws and rules as may apply in various other countries. Pharmacol. 49: 429-437 (2002). • Not available in some countries; not available to some institutions; • PKC412 suppresses Akt activity by blocking serine not available for some uses. phosphorylation in the kinase activation loop and induces apoptosis in myeloma cell lines. Bahlis, N.J. et al., “N-Benzoylstaurosporine (PKC412) inhibits Akt kinase inducing apoptosis in multiple myeloma cells.” Leuk. Lymphoma 46: 899‑908 (2005). • PKC412 selectively inhibits T lymphocyte production of TNF-α; (tumor necrosis factor - alpha) with an IC50 of 0.5 µM. Si, M.S. et al., “Effects of the kinase inhibitor CGP41251 (PKC 412) on lymphocyte activation and TNF-alpha production.” Int. Immunopharmacol. 5: 1141-11419 (2005).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 91 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; IC50 values <40 nM and inhibited cell growth with GI50 values may not be sold for some uses. of 7 to 181 nM in a panel of 14 cell lines representing multiple • Sold for laboratory or manufacturing purposes only; not for tumor types (endometrial, bladder, gastric, breast, lung, and human, medical, veterinary, food, or household use. colon) and containing dysregulated FGFRs. Ponatinib treatment reduced tumor growth and inhibited signaling in all three NH O mouse tumor models examined. Gozgit, J.M. et al., "Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR‑amplified or mutated cancer models." Mol. Cancer Ther. 11: 690‑699 (2012).

N N • In a pivotal phase 2 trial, ponatinib had substantial activity in O heavily pretreated patients and those with refractory T315I. H C H 3 Response rates continued to improve with longer follow-up. CH O Cortes, J.E. et al., "PACE: A pivotal phase II trial of ponatinib in 3 O NCH patients with CML and Ph+ALL resistant or intolerant to dasatinib 3 or nilotinib, or with the T315I mutation." J. Clin. Oncology 2012 ASCO Annual Meeting Proceedings (Post‑Meeting Edition) 30: 6503 (2012). • Ponatinib is the active ingredient in the drug product sold under the trade name Iclusig®. This drug is currently approved in PLX4032 — see Vemurafenib, Free Base at least one country for use in patients with chronic myeloid (Cat. No. V-2800 on page 120). leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). NOTE: THE PMA — see Phorbol 12-Myristate 13-Acetate PONATINIB, FREE BASE RESEARCH COMPOUND SOLD (Cat. No. P-1680 on page 87). BY LC LABORATORIES IS NOT ICLUSIG® AND IS NOT FOR 4α-PMA — see 4α-Phorbol 12-Myristate 13-Acetate HUMAN USE. (Cat. No. P-8880 on page 87). • Related CAS numbers: 1114544-31-8 for the Ponatinib HCl salt. PNU-290940AD – see Sunitinib, Malate Salt (Cat. No. S-8803 on • Another CAS number previously assigned to Ponatinib, Free Base, page 110) and Sunitinib, Free Base (Cat. No. S-8877 on page 109). namely 952306-26-2, has been deleted by CAS and is no longer in use. P-7022 Ponatinib, Free Base, >99% • Sold for laboratory or manufacturing purposes only; not for Synonyms: [AP 24534] human, veterinary, food, or household use. Related Terms: [Iclusig] • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Size US$ ¤ £ ¥ Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 10 mg 45 32 27 5,100 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 25 mg 59 42 35 6,700 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) New! and other common law exemptions of Canadian patent law; (vi) 50 mg 76 55 46 8,600 Section 68B of the Patents Act of 1953 in New Zealand together 100 mg 123 88 74 14,000 with the amendment of same by the Statutes Amendment Bill of 200 mg 182 131 109 20,700 2002; (vii) such related legislation and/or case law as may be or 250 mg 210 151 126 23,900 become applicable in the aforementioned countries; and (viii) such 500 mg 323 232 194 36,700 similar laws and rules as may apply in various other countries. 1 g 570 410 342 64,800 • Not available in some countries; not available to some institutions; 2 g 998 717 599 113,400 not available for some uses.

NOTE: Euro, Pound and Yen prices are revised regularly. H C Please visit www.LCLabs.com for our current prices. 3 H N CH M.W. 532.56 c H F N O [943319-70-8] N 3 29 27 3 6 N N Storage: Store at or below -20 ºC. Solubility: Soluble in O N DMSO at 50 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility N F in plain water is estimated to be about 5-10 µM; buffers, FF serum, or other additives may increase or decrease the aqueous solubility. Disposal: A P-6420 PP1, Free Base, >99% • Ponatinib, also known as AP24534, is a multi-targeted tyrosine Synonyms: [AGL-1872] kinase inhibitor and is active against T315I and other BCR‑ABL Size US$ ¤ £ ¥ mutants. Ponatinib inhibited native BCR‑ABL (IC = 0.37 nM) 50 1 mg 39 28 23 4,400 and the mutants with IC50 values of 2 nM (T315I); 0.44 nM (Q252H); 0.3 nM (Y253F); 0.3 nM (M351T); and 0.34nM New! 5 mg 63 45 38 7,200 (H396P) in biochemical assays. It also inhibited the growth of 10 mg 106 76 64 12,000 Ba/F3 cells with IC50 values of 0.5 nM (Native BCR-ABL), 11 25 mg 252 181 151 28,600 nM (T315I), 2.2 nM (Q252H), 2.8 nM (Y253F), 1.5 nM (M351T), 50 mg 449 323 270 51,000 and 1.1 nM (H396P). It suppressed BCR-ABL (T315I)-driven 100 mg 815 586 490 92,600 tumor growth in mice and completely overcame resistance in 200 mg 1490 1071 895 169,300 cell-based mutagenesis screens. O'Hare, T. et al., "AP24534, a NOTE: Euro, Pound and Yen prices are revised regularly. pan‑BCR‑ABL inhibitor for chronic myeloid leukemia, potently Please visit www.LCLabs.com for our current prices. inhibits the T315I mutant and overcomes mutation-based resistance." Cancer Cell 16: 401‑412 (2009). M.W. 281.36 c16H19N5 [172889-26-8] • Ponatinib inhibited FGFR-mediated signaling and viability Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A with IC50 values <40 nM in Ba/F3 cells engineered to express activated FGFR 1-4, with substantial selectivity over parental • PP1 selectively and potently inhibited the activity of Src Ba/F3 cells. It also inhibited FGFR-mediated signaling with family kinases p56lck and p59fynT with IC50 values of 5 nM

92 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

and 6 nM, respectively. It inhibited anti-CD3-induced T cell PP242 blocks the phosphorylation of Akt at S473 and prevents its tyrosine phosphorylation, TcR-induced T cell proliferation, activation. PP242 inhibits the proliferation of primary cells more and IL-2 gene induction. Hanke, J.H. et al., "Discovery of efficiently than rapamycin. Unlike rapamycin, it also inhibits a novel, potent, and Src family-selective tyrosine kinase cap-dependent translation under conditions. Feldman, M.E. et al., inhibitor. Study of Lck- and FynT-dependent T cell activation." “Active-site inhibitors of mTOR target rapamycin-resistant outputs J. Biol. Chem. 271: 695‑701 (1996). of mTORC1 and mTORC2.” PLoS Biol. 7: 371‑383 (2009). • PP1 has been demonstrated to reduce the expression of vascular • PP242, but not rapamycin, induced death of mouse and human endothelial growth factor (VEGF), protect the blood-brain barrier, leukemia cells in vitro. In vivo, PP242 delayed leukemia onset and reduce brain edema immediately after subarachnoid hemorrhage, enhanced the effects of the front-line tyrosine kinase inhibitors and offer cerebral protection against stroke. Jadhav, V. et al., more effectively than does rapamycin. However, PP242 had "Neuroprotection against surgically induced brain injury." much weaker effects than rapamycin on the proliferation of Surg. Neurol. 67: 15‑20 (2007). normal lymphocytes. Janes, M.R. et al., “Effective and selective • PP1 and its analog, PP2, are powerful inhibitors of TGF- targeting of leukemia cells using a TORC1/2 kinase inhibitor.” β-induced cell migration and invasion in vitro. Both of Nat. Med. 16: 205‑213 (2010). them may prevent metastatic spread in late-stage pancreatic • PP242 inhibited basal serum- and glucocorticoid-inducible ductal adenocarcinoma and non-small cell lung cancer. protein kinase 1 (SGK1) activity and prevented insulin- and Bartscht, T. et al., "The Src family kinase inhibitors PP2 and dexamethasone-induced SGK1 activation, possibly by suppressing PP1 effectively block TGF‑beta1‑induced cell migration and TORC1/2. It inhibited basal Na+ absorption modestly and invasion in both established and primary carcinoma cells." insulin/dexamethasone-induced Na+ transport substantially. Cancer Chemother. Pharmacol. 70: 221‑230 (2012). Mansley, M.K. and Wilson, S.M., “Dysregulation of epithelial + • Another CAS number previously assigned to PP1, Free Base, Na absorption induced by inhibition of the kinases TORC1 and namely 347193-60-6, has been deleted by CAS and is no longer in TORC2.” Br. J. Pharmacol. 161: 1778‑1792 (2010). use. • PP242 inhibited growth and induced apoptosis of multiple • Sold for laboratory or manufacturing purposes only; not for myeloma (MM) cells more effectively than rapamycin. PP242 was human, veterinary, food, or household use. an effective inhibitor of primary MM cells in vitro and growth of 8226 cells in mice. Combining bortezomib with PP242 resulted • This product is offered for R&D use in accordance with (i) 35 in synergistic anti-MM effects. Hoang, B. et al., “Targeting USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese TORC2 in multiple myeloma with a new mTOR kinase inhibitor.” Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Blood 116: 4560‑4568 (2010). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • PP242 significantly augmented histone deacetylase inhibitor- and other common law exemptions of Canadian patent law; (vi) induced apoptosis in hepatocellular carcinoma cells. Shao, H. Section 68B of the Patents Act of 1953 in New Zealand together et al., “Dual targeting of mTORC1/C2 complexes enhances histone with the amendment of same by the Statutes Amendment Bill of deacetylase inhibitor-mediated anti-tumor efficacy in primary 2002; (vii) such related legislation and/or case law as may be or HCC cancer in vitro and in vivo.” J. Hepatol. (Aug 8, 2011– Epub become applicable in the aforementioned countries; and (viii) such ahead of print). similar laws and rules as may apply in various other countries. • In the presence of 100 µM ATP, PP242 inhibits both mTORC1 and • Not available in some countries; not available to some institutions; mTORC2, with IC50 values of 0.03 and 0.058 µM, respectively. not available for some uses. PP242 showed the following IC50 values for inhibition of 22 kinases: CH 3 Kinase [ATP], IC Kinase Form* 50 Ref. Category µM µM NH 2 Abl Tyrosine ? 10 3.6 1 N N DNA-PK Ser/Thr PP 10 0.41 1

N N EGFR Tyrosine CD 10 4.4 1 H C 3 CH EphB4 Tyrosine CD 10 3.4 1 H C 3 3 Hck Tyrosine PP 10 1.2 1 P-6666 PP242, Free Base, >99% JAK2 Tyrosine ** 10 0.11 2 Synonyms: [Torkinib] mTOR Ser/Thr *** 10 0.01 1 mTOR1 Ser/Thr ? 100 0.03 2 Size US$ ¤ £ ¥ mTOR2 Ser/Thr ? 100 0.06 2 10 mg 34 25 20 4,100 p110α Lipid PP 10 2 1 Prices 25 mg 67 49 39 8,100 Reduced! p110β Lipid PP 10 2.2 1 50 mg 121 89 71 14,500 100 mg 223 165 131 26,800 p110γ Lipid PP 10 1.3 1 200 mg 422 312 249 50,700 p110δ Lipid PP 10 0.1 1 250 mg 497 367 293 59,700 PDGFRβ Tyrosine CD 10 0.41 1 500 mg 836 617 493 100,500 PDK1 Ser/Thr PP 10 >10 2 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. PKCα Ser/Thr PP 10 0.05 2 PKCβ I Ser/Thr PP 10 0.2 2 M.W. 308.34 c16H16N6O [1092351-67-1] Storage: Store at or below -20 ºC. Solubility: Soluble in PKCβ II Ser/Thr PP 10 0.19 2 DMSO. Disposal: A RET Tyrosine CD 10 0.22 2 • PP242 is an inhibitor at the kinase domain of the mammalian Src Tyrosine PP 10 1.4 1 target of rapamycin (mTOR), which is a Ser/Thr kinase and a cell growth controller. • PP242 inhibits mTORC1 more effectively than rapamycin. Unlike rapamycin, PP242 inhibits both mTORC1 and mTORC2.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 93 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Src(T338I) Tyrosine PP 10 5.1 1 P-4462 Prostratin, >99% VEGFR2 Tyrosine CD 10 1.5 1 [12-Deoxyphorbol 13-Acetate] [dPAc]

* Form of the enzyme: “PP” = purified protein; Size US$ ¤ £ ¥ “CD” = cytoplasmic domain 1 mg 64 47 40 5,300 ** Amino acid residues 809-1141 5 mg 265 195 164 21,800 *** Amino acid residues 1360-2549 10 mg 468 344 290 38,500 In the two references below, which have the same corresponding 25 mg 995 732 617 81,800 author, conflicting IC values were given for p110γ (IC = 1.3 or NOTE: Euro, Pound and Yen prices are revised regularly. 50 50 Please visit www.LCLabs.com for our current prices. 0.1 µM) and p110δ (IC50 = 1.3 or 0.1 µM), respectively. We have reviewed all the relevant data in the articles and we conclude that M.W. 390.47 C22H30O6 [60857-08-1] the values in the above table are the correct values. WARNING: Highly irritant to skin and mucous membranes. We also note that reference #1 below contains conflicting Storage: Store at or below -20 °C. Solubility: Soluble in statements about the kinase forms used in the table above. DMSO or ethanol. Disposal: A “Materials and Methods” in that reference states that “For IC50 value determinations, purified kinase domains were incubated with • Isolated from strathmore weed (Pimelia prostrata Wild), a New Zealand plant toxic to livestock. Cashmore, A.R. et al. inhibitors...”, whereas Supplementary Table 1 states that “All IC50 values were measured against purified kinases...” After thorough Tetrahedron Lett. 20: 1737-1738 (1976). review of all relevant data in the two references below, in addition • Weak mouse ear irritant, but lethal to mice at 1 µg per mouse. to extensive discussions with technical service at Invitrogen, we Zayed, S. et al. Experientia 33: 1554-1555 (1977). conclude that the forms of the kinases indicated in column 3 of the • Please request Technical Note #5 for additional information. table above are correct. We were unable to make determinations in • This product was previously sold under Cat-No. D-4462 and the the case of three of the kinases, as indicated by question marks in name “12-Deoxyphorbol 13-Acetate”. the table. • Sold for laboratory or manufacturing purposes only; not for 1. Feldman, M.E. et al., “Active-site inhibitors of mTOR target human, medical, veterinary, food, or household use. rapamycin-resistant outputs of mTORC1 and mTORC2.” PLoS Biol. 7: 371‑383 (2009). O

2. Apsel, B. et al., “Targeted polypharmacology: discovery of CH3 dual inhibitors of tyrosine and phosphoinositide kinases.” O

Nat. Chem. Biol. 4: 691‑699 (2008). H3C • Manual docking analyses demonstrated that PP242 was able to fit H H into the TOR model. Sturgill, T.W. and Hall, M.N., “Activating H mutations in TOR are in similar structures as oncogenic mutations OH in PI3KCalpha.” ACS Chem. Biol. 4: 999‑1015 (2009). O OH • NOTE: the term “torkinib” has been used to specify PP242 itself, OH but is also now in use to generically describe compounds that inhibit mTOR at the kinase domain. Protara — see its active ingredient, namely AICAR, Free Base • Sold for laboratory or manufacturing purposes only; not for (Cat. No. A-1098 on page 5). human, veterinary, food, or household use. PS-341 — See Bortezomib, Free Base (Cat. No. B-1408 on page 11). • This product is offered for R&D use in accordance with (i) 35 PTK 787 – see Vatalanib, Dihydrochloride Salt USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese (Cat. No. V-8303 on page 120). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. P-7501 PX-866, >99% Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) [DJM-166] [DJM-2-166] and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Size US$ ¤ £ ¥ with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or 1 mg 59 48 38 4,700 become applicable in the aforementioned countries; and (viii) such 5 mg 135 103 85 11,000 similar laws and rules as may apply in various other countries. 10 mg 189 144 119 15,400 • Not available in some countries; not available to some institutions; 25 mg 359 274 226 29,300 not available for some uses. 100 mg 738 563 465 60,300 300 mg 1590 1214 1001 129,900 OH NOTE: Euro, Pound and Yen prices are revised regularly. H C Please visit www.LCLabs.com for our current prices. 3 N N M.W. 525.59 c H NO [502632-66-8] H C N 29 35 8 3 H Storage: Store at or below -20 °C. Solubility: Soluble in N NH 2 DMSO at 200 mg/mL; soluble in ethanol at 200 mg/mL; N very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, PR-171 — see Carfilzomib, Free Base (Cat. No. C-3022 on page 18). or other additives may increase or decrease the aqueous Prograf — see its active ingredient, namely FK-506 solubility. Disposal: A (Cat. No. F-4900 on page 42). • PX-866, a derivative of wortmannin, potently inhibited purified phosphoinositide (PtdIns)-3-kinase (IC50 = 0.1 nM) and PtdIns-3- kinase signaling (IC50 = 20 nM) as assessed by phospho-Ser473- Akt levels in HT-29 colon cancer cells. PX-866 showed antitumor activity in vivo against s.c. A-549 human lung cancer xenografts and OvCar-3 human ovarian cancer in immunodeficient mice. PX- 866 also enhanced the antitumor activity of cisplatin against A-549

94 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

xenografts and radiation treatment against OvCar-3 xenografts. Ihle, N.T. et al., “Molecular pharmacology and antitumor activity Q-4747 Quizartinib, Free Base, >99% of PX-866, a novel inhibitor of phosphoinositide-3-kinase Synonyms: [AC220] [AC010220] signaling.” Mol. Cancer Ther. 3: 763-772 (2004). Size US$ ¤ £ ¥ • PX-866 appears to inhibit tumor growth by blocking the phosphatidylinositol 3-kinase (PI3K) pathway and cell 5 mg 59 44 35 7,100 motility. Howes A.L. et al., “The phosphatidylinositol 3-kinase Prices 10 mg 82 61 48 9,900 inhibitor, PX-866, is a potent inhibitor of cancer cell motility Reduced! 25 mg 175 129 103 21,000 and growth in three-dimensional cultures.” Mol. Cancer Ther. 50 mg 264 195 156 31,700 6: 2505‑2514 (2007). 100 mg 432 319 255 51,900 • Hyperglycemia is a side effect of PX-866 treatment. Combination 200 mg 634 468 374 76,200 treatment of peroxisome proliferator-activated receptor γ agonist 250 mg 835 617 492 100,400 pioglitazone with PX-688 can overcome the increase in blood 500 mg 1340 990 790 161,100 glucose without affecting antitumor activity caused by PX-866. 1 g 1970 1455 1161 236,800 Ihle N.T. et al., “Peroxisome proliferator-activated receptor NOTE: Euro, Pound and Yen prices are revised regularly. gamma agonist pioglitazone prevents the hyperglycemia caused Please visit www.LCLabs.com for our current prices. by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity.” Mol. Cancer Ther. M.W. 560.67 C29H32N6O4S [950769-58-1] 8: 94-100 (2009). Storage: Store at or below -20 ºC. Solubility: Soluble • PX-866 is a PI3-K inhibitor with selectivity for p110α. It in DMSO at 200 mg/mL; very poorly soluble in ethanol; enhanced the antitumor activity of gefitinib against A-549 non- very poorly soluble in water; maximum solubility in plain small cell lung cancer (NSCLC) xenografts, giving complete water is estimated to be about 10-20 µM; buffers, serum, tumor growth control during the early stages of treatment. Ihle or other additives may increase or decrease the aqueous N.T. et al., “The phosphatidylinositol-3-kinase inhibitor PX-866 solubility. Disposal: A overcomes resistance to the epidermal growth factor receptor • Quizartinib, also known as AC-220, is a second-generation FLT3 inhibitor gefitinib in A-549 human non-small cell lung cancer receptor tyrosine kinase inhibitor. xenografts.” Mol. Cancer Ther. 4: 1349-1357 (2005). • Quizartinib has high affinity for FLT3 in a binding • STRUCTURE NOTE: Chemical Abstracts Service defines PX-866 assay (Kd = 1.6 nM) and is a potent inhibitor in cellular as having the “E” configuration for the enamine double bond at autophosphorylation assays (IC50 = 1.1 nM for FLT3-ITD and the lower left corner of the structure. At least one other vendor’s 4.2 nM for wt FLT3). It inhibits the growth of human leukemia structure for PX-866 has the incorrect “Z” configuration for that cell line MV4-11 (IC50 = 0.56 nM) which is FLT3 dependent double bond. and contains a homozygous FLT3-ITD mutation, and A375 cells • Sold for laboratory or manufacturing purposes only; not for (IC50 > 10,000 nM) which are not FLT3 dependent and contain an human, medical, veterinary, food, or household use. activating mutation in BRAF. Quizartinib inhibits FLT3 activity • This product is offered for R&D use in accordance with (i) 35 in subcutaneous MV4-11 tumor xenografts. Treatment with USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese quizartinib at 10 mg/kg in MV4-11 tumor xenografts results in Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent rapid and complete regression of tumors. Quizartinib prolongs the Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. survival of mice injected with MV4-11 cells in a dose-dependent Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) manner. Zarrinkar, P.P. et al., “AC220 is a uniquely potent and and other common law exemptions of Canadian patent law; (vi) selective inhibitor of FLT3 for the treatment of acute myeloid Section 68B of the Patents Act of 1953 in New Zealand together leukemia (AML).” Blood 114: 2984‑2992 (2009). with the amendment of same by the Statutes Amendment Bill of • Quizartinib inhibited the autophosphorylation of wt FLT3 and 2002; (vii) such related legislation and/or case law as may be or FLT3/ITD with IC50 values of 5 and 1 nM, respectively. However, become applicable in the aforementioned countries; and (viii) such the cytotoxic effect of quizartinib was not exclusively dependent similar laws and rules as may apply in various other countries. on inhibition of FLT3 autophosphorylation. It depended on the • Not available in some countries; not available to some institutions; clinical status of acute myoloid leukemia and FLT3-mutant not available for some uses. allelic burden. Relapsed samples and samples with a high mutant allelic burden were more sensitive to the cytotoxic effect from

CH O FLT3 inhibition by quizartinib compared with the samples 3 AcO H C O obtained at diagnosis or those with a low mutant allelic burden. 3 CH 3 Pratz, K.W. et al., “FLT3-mutant allelic burden and clinical O status are predictive of response to FLT3 inhibitors in AML.” H Blood 115: 1425‑1432 (2010). O O • Quizartinib has demonstrated significant promise in early OH phases of clinical investigation with patients with acute myeloid N leukemia (AML), and is now in more advanced clinical trials. Fathi, A.T. and Chabner, B.A., “FLT3 Inhibition as Therapy in Acute Myeloid Leukemia: A Record of Trials and Tribulations.” The Oncologist 16: 1162‑1174 (2011). 1,9-Pyrazoloanthrone — See SP600125 (Cat. No. S-7979 on page 107). • After intensive chemotherapy, plasma FLT3 ligand levels rose significantly in acute myeloid leukemia patients, which interfered with the cytotoxicity of quizartinib. Sato, T. et al., “FLT3 ligand P-7501-2009-10-15-kedREV.SKC impedes the efficacy of FLT3 inhibitors in vitro and in vivo.” Blood 117: 3286‑3293 (2011). • Related CAS numbers: 1132827-21-4 for the quizartinib dihydrochloride. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 95 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. signalling by the 70 kd S6 protein kinases.” J. Chung et al., Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Cell 69: 1227 (1992). and other common law exemptions of Canadian patent law; (vi) • Lymphokine-induced cell proliferation at the G1 phase is inhibited Section 68B of the Patents Act of 1953 in New Zealand together and apoptosis in a murine B cell line is induced by rapamycin. with the amendment of same by the Statutes Amendment Bill of Rapamycin arrests the Saccharomyces cerevisiae cell cycle 2002; (vii) such related legislation and/or case law as may be or irreversibly in the G1 phase., “Rapamycin-induced inhibition of become applicable in the aforementioned countries; and (viii) such p34cdc2 kinase activation is associated with G1/S-phase growth similar laws and rules as may apply in various other countries. arrest in T lymphocytes.” W.G. Morice et al., J. Biol. Chem. • Not available in some countries; not available to some institutions; 268: 3734 (1993)., “Inhibition of T and B lymphocyte proliferation not available for some uses. by rapamycin.” J.E. Kay et al., Immunology 72: 544 (1991)., “Targets for cell cycle arrest by the immunosuppressant rapamycin O S N in yeast.” J. Heitman et al., Science 253: 905 (1991). O N N • Rapamycin extended median and maximal lifespan of both male and female mice when fed late in life. Harrison, D.E. O N O et al., “Rapamycin fed late in life extends lifespan in genetically CH 3 heterogeneous mice.” Nature 460: 392‑395 (2009). N CH N 3 CH • Rapamycin has shown activity in slowing cellular and organismal 3 H H aging. Rapamycin abolished nuclear blebbing, delayed the R-115777 – see Tipifarnib, Free Base (Cat. No. T-9104 on page 112). start of cellular senescence, and improved the degradation of progerin in Hutchinson-Gilford progeria syndrome fibroblast R7204 — see Vemurafenib, Free Base (Cat. No. V-2800 on page 120). cells. It also reduced the formation of insoluble progerin aggregates and resulted in clearance through autophagic RAD001 – see Everolimus (Cat. No. E-4040 on page 40). mechanisms in normal fibroblasts. Cao, K. et al., “Rapamycin Ramihyphin A – see Cyclosporin A (Cat. No. C-6000 on page 25). reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.” RAPA – see Rapamycin (Cat. No. R-5000 on page 96). Sci. Transl. Med. 3: 89ra58 (2011). Rapamune – see its active ingredient, namely Rapamycin • Due to a different mechanism of action from cyclosporin and (Cat. No. R-5000 on page 96). FK-506, rapamycin may prove to be important in organ transplant patient therapy. Fewer side effects than the standard anti-rejection R-5000 Rapamycin, >99% treatments have been observed. Proliferation of activated T cells, [AY-22989] [LCP-Siro] [RAPA] [Rapamune] [SILA but not apoptosisis, is blocked by rapamycin. The induction 9268A] [Sirolimus] of apoptosis of rejection-causing T cells reduces the tendency towards transplant rejection., “The future role of target of Size US$ ¤ £ ¥ rapamycin inhibitors in renal transplantation.” C. Schwarz and 50 mg 53 40 34 4,100 R. Oberbauer Curr Opin Urol. 12: 109 (2002)., “Requirement for T-cell apoptosis in the induction of peripheral transplantation 100 mg 69 51 44 5,400 tolerance.” A.D. Wells et al., Nat Med. 5: 1303 (1999)., “Blocking 200 mg 119 89 76 9,300 both signal 1 and signal 2 of T-cell activation prevents apoptosis of 250 mg 132 99 85 10,300 alloreactive T cells and induction of peripheral allograft tolerance.” 300 mg 156 116 100 12,200 Y. Li et al. Nat Med. 5: 1298 (1999). 500 mg 225 168 144 17,600 • We have had one lot of Selleck Chemical’s rapamycin analyzed by 1 g 415 310 266 32,400 a highly experienced and expert clinical analytical laboratory that 2 g 754 563 483 58,800 specializes in rapamycin analyses. Using liquid chromatography 5 g 1425 1063 913 111,200 - mass spectrometry, they found a purity of 96.7% (cis plus trans) 10 g 2650 1978 1699 206,800 for a lot of Selleck’s rapamycin. In contrast, we have proven NOTE: Euro, Pound and Yen prices are revised regularly. our rapamycin to be greater than 99% in purity for every lot, no Please visit www.LCLabs.com for our current prices. exceptions. • Formulations for in vivo administration. Researchers wishing to M.W. 914.17 C51H79NO13 [53123-88-9] M.I. 14: 8114 administer rapamycin in vivo may find the following references useful, particularly as a source of information about formulations Storage: Store at or below -20 °C. Solubility: Soluble in of rapamycin in various vehicles that have been used for i.p., i.m. DMSO at 200 mg/mL; soluble in ethanol at 50 mg/mL; and i.v. administration: very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-20 µM; buffers, serum, 1. Circulation 99: E1080-E1087 (1999). or other additives may increase or decrease the aqueous Carboxymethylcellulose, polysorbate 80; i.m. solubility. Disposal: A 2. Proc. Natl. Acad. Sci. USA 96: 8657-8662 (1999). Dimethylacetamide, PEG 400, polyoxyethylene sorbitan • Trusted Worldwide: more than 10,000 vials of our rapamycin monooleate; i.p. have been shipped to more than 2,500 laboratories worldwide since 2002. 3. Am. J. Physiol. Endocrin. Metab. 279: E1080-E1087 (2000). 5% DMSO, i.v. • Available in gram to kilogram quantities—request a bulk quote. 4. Blood 100: 1084-1087 (2002). PEG 300, polysorbate and • Immunosuppressant, related to FK-506, but without calcineurin ethanol; i.p. inhibitory activity even when complexed to FK-506 binding protein. Selectively blocks signalling that leads to p70 S6 kinase 5. Cancer Res. 62: 7291-7297 (2002). Ethanol, Tween 80; i.p. • See also our other standard immunosuppresent products: activation (IC50 = 50 pM)., “Failure of rapamycin to block proliferation once resting cells have entered the cell cycle despite - Cyclosporin (Cat. No. C-6000 on page 25) inactivation of p70 S6 kinase.” Terada, N. et al., J. Biol. Chem. - FK-506 (Cat. No. F-4900 on page 42) 268: 12062 (1993)., “Dissociation of pp70 ribosomal protein S6 kinase from insulin-stimulated glucose transport in 3T3-L1 • Rapamycin is the active ingredient in the drug sold under the trade name Rapamune®. NOTE: The rapamycin product sold by LC adipocytes.” D.C. Fingar et al., J. Biol. Chem. 268: 3005 (1993)., ® “Rapamycin-induced inhibition of the 70-kilodalton S6 protein Laboratories is NOT Rapamune and is NOT for human use. kinase.” Price, D.J. et al., Science 257: 973 (1992)., “Rapamycin- • Sold for laboratory or manufacturing purposes only; not for FKBP specifically blocks growth-dependent activation of and human, medical, veterinary, food, or household use.

96 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

HO R-8765 Resiniferonol 9,13,14-Orthophenylacetate, >99% [ROPA] CH O 3 CH 3 Size US$ ¤ £ ¥ 1 mg 39 27 24 3,700 O O OH N 5 mg 127 89 77 12,000 O O O CH O 10 mg 239 167 145 22,600 O 3 HO 25 mg 515 359 312 48,600 O OCH 3 100 mg 1675 1168 1015 158,100 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices.

M.W. 464.55 c28H32O6 [57852-42-3] Recentin — see its active ingredient, namely WARNING: Highly irritant to skin and mucous membranes. Cediranib, Free Base (Cat. No. C-4300 on page 19). SPECIAL HAZARD: TUMOR PROMOTER. Gloves and mask should be worn when using this compound. Care R-6712 Resiniferatoxin, >99% must be taken to prevent contact through all routes of [RTX] exposure. Storage: Store at or below -20 °C. Solubility: Soluble in Size US$ ¤ £ ¥ DMSO or ethanol. Disposal: A 1 mg 55 40 35 4,200 • 20-Deacylated derivative of resiniferatoxin and tinyatoxin. Not 5 mg 178 129 113 13,700 active as a capsaicin analog. 10 mg 340 246 215 26,100 • Binds to and activates protein kinase C, with high potency. 25 mg 725 525 459 55,700 • Useful as starting material for synthesis of resiniferatoxin analogs. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. • Please request Technical Note #28 for additional information. M.W. 628.71 C H O [57444-62-9] • Sold for laboratory or manufacturing purposes only; not for 37 40 9 human, medical, veterinary, food, or household use. WARNING: Highly irritant to skin and mucous membranes. SPECIAL HAZARD: POTENT NEUROTOXIN. Gloves and mask should be worn when using this compound. Care

must be taken to avoid contact via all routes of exposure O H C O Storage: Store at or below -20 ºC (see below). 3 O H H Solubility: Soluble in DMSO or ethanol. Disposal: A • Extremely potent analog of capsaicin, the major active principle of common red pepper. Szallasi, A. and Blumberg, P.M. HO OH Neuroscience 30: 515-520 (1989). O • STABILITY AND STORAGE: Resiniferatoxin (RTX) is susceptible to slow degradation if exposed to air. Even at -20 ºC, RG7204 — see Vemurafenib, Free Base (Cat. No. V-2800 on page 120). RTX will develop a few tenths of a percent of impurities over a R-7040 Ridaforolimus, >99% period of several months if air is not rigorously excluded. Thus, RTX must be stored in an inert atmosphere for long-term stability. [9CI] [AP 23573] [Deforolimus] [MK-8669] All of our catalog sizes (1, 5, 10, and 25 mg) are flame-sealed under nitrogen or argon in Type I Borosilicate glass ampules. Size US$ ¤ £ ¥ Under these conditions RTX is stable for many years. Once 5 mg 39 29 25 3,000 removed from the original ampule, for best long-term storage it 10 mg 56 42 36 4,400 is recommended that RTX be stored at -20 ºC or colder in a very 25 mg 125 94 81 9,700 tightly sealed container with an inert atmosphere such as nitrogen 50 mg 198 149 128 15,400 or argon. Note that a screw-cap container would require a melted 100 mg 335 253 217 26,100 wax seal to prevent slow loss of the inert gas and entry of air. Very 200 mg 448 338 290 34,800 few types of container closures other than flame-sealed glass are truly airtight. 500 mg 898 678 581 69,800 1 g 1390 1049 900 108,100 • CAUTION: RTX in powdered form is extremely irritant to the NOTE: Euro, Pound and Yen prices are revised regularly. eyes, mucous membranes and lungs. Handling RTX in powdered Please visit www.LCLabs.com for our current prices. form should be avoided if at all possible. If the powdered form must be handled, full face, respiratory and body protection should M.W. 990.21 c53H84NO14P [572924-54-0] be worn. Storage: Store at or below -20 °C. Solubility: Soluble in • Please request Technical Note #28 for additional information. DMSO. Disposal: A • Pharmaceutical formulations containing this compound, and anti- • Ridaforolimus (the name has been changed from “deforolimus”) is inflammatory, anti-viral and anti-psoriatic uses, are covered by an immunosupressant and a novel small-molecule inhibitor of the U.S. patents 5,643,948 and 5,955,501. protein mammalian target of rapamycin (mTOR). Ridaforolimus • Sold for laboratory or manufacturing purposes only; not for inhibits cancer cell growth, cell division, metabolism, and human, medical, veterinary, food, or household use. angiogenesis by blocking mTOR. Mahalingam D. et al., “Targeting the mTOR pathway using deforolimus in cancer therapy.” Future Oncol. 5: 291-303 (2009). • Ridaforolimus had an antitumor activity in >85% of patients with O advanced solid tumors. Rivera V.M. et al., “Pharmacodynamic H C 3 OO study of skin biopsy specimens in patients (pts) with refractory or H H OH advanced malignancies following administration of AP23573, an O mTOR inhibitor.” 2005 ASCO Annual Meeting.

O OCH OH 3 O

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 97 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Ridaforolimus has low toxicity profiles and promising clinical • RITA (an abbreviation for "reactivation of p53 and induction of efficacy in patients with advanced sarcomas. Chawla, S.P. et al., tumor cell apoptosis") is an activator of the p53 tumor suppressor “Updated results of a phase II trial of AP23573, a novel mTOR protein. It showed p53-dependent antitumor effect in vivo. inhibitor, in patients (pts) with advanced soft tissue or bone Issaeva, N. et al., "Small molecule RITA binds to p53, blocks sarcomas.” J. Clin. Oncol. 24: 9505 (2006). p53‑HDM‑2 interaction and activates p53 function in tumors." • The level of phosphorylated S6 ribosomal protein expression was Nat. Med. 10: 1321‑1328 (2004). a marker of early tumor response to ridaforolimus. Iwenofu, O.H. • RITA significantly inhibited the growth of renal carcinoma cell et al., “Phospho-S6 ribosomal protein: a potential new predictive lines and induced apoptosis, possibly either by inducing DNA sarcoma marker for targeted mTOR therapy.” Mod. Pathol. damage or by inducing both DNA-protein and DNA‑DNA 21: 231‑237 (2008). cross‑links without detectable DNA single-strand breaks. • MEK inhibitors in combination with the mTOR inhibitor, Nieves‑Neira, W. et al., "DNA protein cross-links produced by rapamycin or its analogue ridaforolimus, exhibited synergism in NSC 652287, a novel thiophene derivative active against human human lung cancer cell lines by inhibiting proliferation rather renal cancer cells." Mol. Pharmacol. 56: 478‑484 (1999). than promoting cell death. Legrier M.E. et al., “Targeting protein • RITA had anti-tumor activity against chronic lymphocytic translation in human non small cell lung cancer via combined leukemia, acute myeloid leukemia, multiple myeloma, MEK and mammalian target of rapamycin suppression.” and mantle cell lymphoma. Saha, M.N. et al., "Targeting Cancer Res. 67: 11300-11308 (2007). p53 by small molecules in hematological malignancies." • Another CAS number previously assigned to ridaforolimus, J. Hematol. Oncol. 6: 23 (2013). 697252-87-2, has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; • Not available in some countries; not available to some institutions; not available for some uses. not available for some uses. S S O HO O OH Me O P Me Ro 09-1978 — see Capecitabine (Cat. No. C-2799 on page 17). MeO Me Me Ro 09-1978/000 — see Capecitabine (Cat. No. C-2799 on page 17). Ro 22-4667 — see Fenretinide (Cat. No. F-4077 on page 41). O O OH N Me Ro 50-8231 — see Erlotinib, Free Base (Cat. No. E-4997 on page 37). O O O O MeO RO5185426 — see Vemurafenib, Free Base HO Me (Cat. No. V-2800 on page 120). O OMe Me Rolazar — see Pemetrexed, Disodium Salt, Heptahydrate (Cat. No. P-7177 on page 84). Me Me R-2020 (R,S)-Rolipram, >99% Ridorubicin — see Epirubicin, Hydrochloride Salt Synonyms: [Adeo] [ME-3167] [SB 95952] [ZK-62711] (Cat. No. E-8000 on page 35). RIIR-7040-2009-10-08-kedREV.SKC retinamide — see Fenretinide (Cat. No. F-4077 on page 41). Size US$ ¤ £ ¥ 10 mg 37 29 24 4,100 R-7117 RITA, >99% 25 mg 51 39 34 5,700 Synonyms: [p53 Activator III] 50 mg 67 52 44 7,500 100 mg 98 76 65 11,000 Size US$ ¤ £ ¥ 300 mg 234 181 155 26,200 5 mg 49 35 29 5,600 1 g 585 452 387 65,400 New! 10 mg 83 60 50 9,400 2 g 924 714 611 103,300 25 mg 122 88 73 13,900 5 g 1425 1102 942 159,300 50 mg 192 138 115 21,800 NOTE: Euro, Pound and Yen prices are revised regularly. 100 mg 268 193 161 30,400 Please visit www.LCLabs.com for our current prices.

250 mg 548 394 329 62,300 M.W. 275.34 C16H21NO3 [61413-54-5] 500 mg 944 679 567 107,200 M.I. 14: 8251 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 50 mg/mL; soluble in ethanol at 25 mg/mL with M.W. 292.37 C14H12O3S2 [213261-59-7] warming; very poorly soluble in water; maximum solubility Storage: Store at or below -20 ºC. Solubility: Soluble in in plain water is estimated to be about 50-100 µM; buffers, DMSO. Disposal: A serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

98 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• Rolipram is a selective phosphodiesterase 4 (PDE4) inhibitor. ROPA — see Resiniferonol 9,13,14-Orthophenylacetate PDE4 enzymes inactivate cyclic AMP (cAMP) via hydrolysis to (Cat. No. R-8765 on page 97). 5'-AMP. • Rolipram has two enantiomeric forms, R(-) and S(+). This product Rosamox — see its active ingredient, namely Carnosic Acid, is the racemic mixture of the two enantiomers. Free Acid (Cat. No. C-2662 on page 18). • R-(-)-rolipram demonstrated a higher affinity for the PDE4 R-1234 Roscovitine, Free Base, >99% enzyme than S-(+)-rolipram, by about 8-fold in vitro and about 12- to 15-fold in vivo. Parker, C.A. et al., “Behaviour of [11C] [CYC202] [Seliciclib] R(-)- and [11C]S(+)-rolipram in vitro and in vivo, and their Size US$ ¤ £ ¥ use as PET radiotracers for the quantificative assay of PDE4.” Synapse 55: 270‑279 (2005). 10 mg 58 47 37 4,600 • Rolipram is able to reverse ischemia-reperfusion (I/R)- 25 mg 82 63 52 6,700 induced increased microvascular permeability through cAMP 50 mg 153 117 96 12,500 phosphodiesterase (PDE) isozyme-selective inhibition. 100 mg 214 163 135 17,500 Barnard, J.W. et al., “Reversal of pulmonary capillary ischemia- 200 mg 287 219 181 23,400 reperfusion injury by rolipram, a cAMP phosphodiesterase 300 mg 399 305 251 32,600 inhibitor.” J. Appl. Physiol. 77: 774‑781 (1994). 1 g 927 708 584 75,700 • Rolipram reduced the initial and late response to ovalbumin 2 g 1590 1214 1001 129,900 (OVA) in isolated strips of guinea-pig colonic smooth muscle. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. For both responses, the (S)-isomer (EC50 = approximately 1.0 µM) was about 10 fold less potent than the (R)-isomer M.W. 354.45 c H N O [186692-46-6] (EC = approximately 0.1 µM). Grous, M. and Barnette, M., 19 26 6 50 M.I. 14: 10240 “Prevention by phosphodiesterase inhibitors of antigen- induced contraction of guinea-pig colonic smooth muscle.” Storage: Store at or below -20 °C. Solubility: Prepare Br. J. Pharmacol. 111: 259‑263 (1994). initial stock solutions in DMSO (soluble at 200 mg/mL) or ethanol (soluble at 200 mg/mL) for in vitro use; solubility • Rolipram suppressed cardiopulmonary bypass-induced in water is low. Appearance: White to off-white powder; systemic inflammatory response syndrome, probably through mp 106-107 °C. Disposal: A the regulation of proinflammatory mediators by inhibiting cdc2 phosphodiesterase type 4. Hamamoto, M. et al., “Suppressive • Roscovitine is a potent inhibitor of p34 (IC50 = 0.2 µM). effect of phosphodiesterase type 4 inhibition on systemic Also inhibits p33cdk2 and p33cdk5. Havlicek, L. et al., inflammatory responses after cardiopulmonary bypass.” J. Med. Chem. 40: 408‑412 (1997). J. Artif. Organs 9: 144‑148 (2006). • Note: The word “roscovitine” inherently means the R-Isomer. • R6/2 mutant mice recapitulate human Huntington’s disease • Sold for laboratory or manufacturing purposes only; not for in many ways. Rolipram has a neuroprotective effect in these human, medical, veterinary, food, or household use. mice. After treatment with rolipram, R6/2 mice survived • This product is offered for R&D use in accordance with (i) 35 longer and displayed less severe signs of neurological USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese dysfunction. DeMarch, Z. et al., “Beneficial effects of Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent rolipram in the R6/2 mouse model of Huntington’s disease.” Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Neurobiol. Dis. 30: 375‑387 (2008). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • Dopamine plays an essential role in the regulation of motor and and other common law exemptions of Canadian patent law; (vi) cognitive functions. The effect of dopamine largely depends on Section 68B of the Patents Act of 1953 in New Zealand together the cAMP/PKA signaling cascade. Rolipram shows utility in with the amendment of same by the Statutes Amendment Bill of neuropsychiatric and neurodegenerative disorders, posisbly by 2002; (vii) such related legislation and/or case law as may be or affecting dopamine neurotransmission. Nishi, A. et al., “Distinct become applicable in the aforementioned countries; and (viii) such roles of PDE4 and PDE10A in the regulation of cAMP/PKA similar laws and rules as may apply in varous other countries. signaling in the striatum.” J. Neurosci. 28: 10460‑10471 (2008). • Another CAS number previously assigned to rolipram, namely 85416-74-6, has been deleted by CAS and is no longer in use. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. HN • This product is offered for R&D use in accordance with (i) 35 N N USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese HO Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent N N N Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. H Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together RoseOx — see its active ingredient, namely Carnosic Acid, Free Acid (Cat. No. C-2662 on page 18). with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or R-9630 Rottlerin, >98% become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. [Mallotoxin] • Not available in some countries; not available to some institutions; (This product and its support have been discontinued not available for some uses. for the reasons noted below)

O H N M.W. 516.54 c30H28O8 [82-08-6] M.I. 14: 8272 NOTE: Rottlerin has been referred to as a specific inhibitor of PKCδ, but this appears to be incorrect for the following reasons: O

OCH 3

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 99 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• An excellent and very thorough review of the numerous and Rubex — see its active ingredient, namely Doxorubicin, confounding biological activities of rottlerin is now available: Hydrochloride Salt (Cat. No. D-4000 on page 33) and Soltoff, Stephen P., “Rottlerin: an inappropriate and ineffective Doxorubicin, Free Base (Cat. No. D-4099 on page 32). inhibitor of PKCδ.” Trends Pharm. Sci. 28: 453-458 (2007). This review makes it clear that, unfortunately, there may now be R-6600 Ruxolitinib, Free Base, >99% hundreds of published articles that contain erroneous, rottlerin- Synonyms: [INCB018424] [INCB18424] [NCB018424] based conclusions about PKC functions. δ [NCB18424] • Initially, rottlerin was reported to inhibit PKCδ (IC50 = 3-6 µM) 5- to 10-fold more potently than PKCα or PKCβ and 13- to 33-fold Size US$ ¤ £ ¥ more potently than PKCε, ζ, or η. It also inhibited CAM kinase 5 mg 51 38 30 6,100 III at 3-6 µM, was inactive against SRC kinase, and was a weak Prices 10 mg 82 61 49 9,900 inhibitor of PKA and casein kinase II. Biochem. Biophys. Res. Reduced! Comm. 199: 93-98 (1994). 25 mg 139 104 83 16,700 • At best, these potency differences of 5- to 13- fold are quite 50 mg 185 138 110 22,300 modest, pharmacologically speaking, and in practice would require 100 mg 341 254 203 41,100 careful manipulation of concentrations to produce meaningful 200 mg 646 482 385 77,800 differentiation of PKC isotype effects. 500 mg 1450 1081 864 174,700 • Much more serious problems with rottlerin have come to light. In NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. an extensive study of protein kinases and inhibitors, rotterlin failed to show any PKC inhibitory activity at all against the α and δ PKC M.W. 306.37 C17H18N6 [941678-49-5] isotypes, even at 20 µM and very low ATP concentrations and [1160597-27-2] under a variety of conditions. It was, however, a potent inhibitor of Storage: Store at or below -20 ºC. Solubility: Soluble in MAPK-activated protein kinase 2, p38-regulated/activated kinase, DMSO at 28 mg/mL; soluble in ethanol at 15 mg/mL with protein kinase A, and glycogen synthase kinase 3-beta. Biochem. J. warming; very poorly soluble in water; maximum solubility 351: 95-105 (2000). Thus, rottlerin does not appear to have any in plain water is estimated to be about 25-50 µM; buffers, utility as a PKCδ-selective tool. serum, or other additives may increase or decrease the • Furthermore, rottlerin has been shown to be an uncoupler aqueous solubility. Disposal: A of mitochondrial oxidative phosphorylation. J. Biol. Chem. • This is the free base form of ruxolitinib, also known as 276: 37986‑37992 (2001) and Endrocrinology 143: 3884‑3896 INCB18424; please see the other form of this product, Ruxolitinib, (2002). This effect results in additional non-specific, confounding Phosphate Salt (Cat. No. R-6688 on page 101), for further technical activities for rottlerin. Cancer Res. 63: 5118‑5125 (2003). information. The phosphate salt form of ruxolitinib is used for • LC Labs™ has tested the purity of rottlerin obtained from the some or all ruxolitinib formulations for use in humans. same source used in the BBRC article cited above, and many • This ruxolitinib product research compound is the free base, substantial impurities were found. Our highly purified product whose CAS number is given above. The CAS number of the was free of these impurities, and we believe the rottlerin used in phosphate salt is 1092939-17-7. the Biochem. J. study is traceable to LC Labs™. Thus, the original inhibitory activity of rottlerin for PKCδ may have been due to an • As of September 2011, it appears that Chemical Abstracts Service impurity not present in the later study. currently also has a second CAS number for Ruxolitinib, Free Base, namely 1160597-27-2. • There are now many published studies that cite the effects of rottlerin as a basis for conclusions about the cellular roles of • Another CAS number previously assigned to Ruxolitinib, Free PKCδ. These conclusions now appear to be incorrect. We would Base, namely 1138325-12-8, has been deleted by CAS and is no appreciate receiving from our readers any information that longer in use. might shed more light on this topic, so that we can inform other • Ruxolitinib (as the phosphate salt) is the active ingredient in the researchers of the latest findings regarding rottlerin’s actual drug sold under the trade name Jakafi® by Incyte Corporation. biological properties. Jakafi® is currently approved in at least one country for use in • In the past, we produced rottlerin by purifying it from raw material patients with intermediate or high-risk myelofibrosis, including from a source in Europe, but that source no longer sells crude primary myelofibrosis, post-polycythemia vera myelofibrosis rottlerin. Given the highly questionable utility of rottlerin as a and post-essential thrombocythemia myelofibrosis. NOTE: kinase inhibitor, we decided not to pursue alternative sources of THE RUXOLITINIB, FREE BASE RESEARCH COMPOUND ® raw materials. Therefore, we have now discontinued all sales of SOLD BY LC LABORATORIES IS NOT JAKAFI AND IS ® rottlerin. NOT FOR HUMAN USE. Jakafi is a registered trademark of Incyte Corporation. LC Laboratories is not affiliated with Incyte Corporation, and the ruxolitinib research compounds sold by LC Laboratories are not manufactured by Incyte Corporation. • Sold for laboratory or manufacturing purposes only; not for O human, medical, veterinary, food, or household use. HO OH HO O • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese O Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. OH OH Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Rozevin sulfate — see its active ingredient, namely Vinblastine, Section 68B of the Patents Act of 1953 in New Zealand together Sulfate Salt (Cat. No. V-7300 on page 121). with the amendment of same by the Statutes Amendment Bill of RP 54780 — see Oxaliplatin (Cat. No. O-7111 on page 79). 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such RP 56976 — see Docetaxel (Cat. No. D-1000 on page 29). similar laws and rules as may apply in various other countries. RPR-116258 — see Cabazitaxel (Cat. No. C-2581 on page 15). • Not available in some countries; not available to some institutions; not available for some uses. RTX — see Resiniferatoxin (Cat. No. R-6712 on page 97).

100 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

CN • Ruxolitinib inhibited JAK1 and JAK2, with IC50 values of 5.9 nM and 5.7 nM, respectively. It inhibited IL-6 and IL- 23 effects at concentrations less than 50 nM. Ruxolitinib N N was effective in the rat adjuvant arthritis model and multiple murine models of arthritis. Fridman, J.S. et al., “Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.” N J. Immunol. 184: 5298‑5307 (2010).

N • Ruxolitinib had intriguing results in patients with rheumatoid N arthritis and psoriasis by inhibiting inflammatory cytokine H signaling, possibly through JAK1 suppression. Mesa, R.A., “Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the R-6688 Ruxolitinib, Phosphate Salt, >99% treatment of myeloproliferative neoplasms and psoriasis.” Synonyms: [INCB018424] [INCB18424] [NCB018424] IDrugs 13: 394‑403 (2010). [NCB18424] • This ruxolitinib product is the phosphate salt, whose CAS Related Terms: [Jakafi] number is given above. The CAS number of the free base form of ruxolitinib is 941678-49-5. Size US$ ¤ £ ¥ • Ruxolitinib phosphate is the active ingredient in the drug sold 5 mg 51 38 30 6,100 under the trade name Jakafi® by Incyte Corporation. Jakafi® Prices 10 mg 82 61 49 9,900 is currently approved in at least one country for use in patients Reduced! 25 mg 139 104 83 16,700 with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and 50 mg 185 138 110 22,300 post-essential thrombocythemia myelofibrosis. NOTE: THE 100 mg 341 254 203 41,100 RUXOLITINIB, PHOSPHATE SALT RESEARCH COMPOUND 200 mg 646 482 385 77,800 SOLD BY LC LABORATORIES IS NOT JAKAFI® AND IS 500 mg 1450 1081 864 174,700 NOT FOR HUMAN USE. Jakafi® is a registered trademark of NOTE: Euro, Pound and Yen prices are revised regularly. Incyte Corporation. LC Laboratories is not affiliated with Incyte Please visit www.LCLabs.com for our current prices. Corporation, and the ruxolitinib research compounds sold by M.W. 404.36 c17H18N6•H3O4P [1092939-17-7] LC Laboratories are not manufactured by Incyte Corporation. Storage: Store at or below -20 ºC. Solubility: Soluble • Sold for laboratory or manufacturing purposes only; not for in DMSO at 200 mg/mL; very poorly soluble in ethanol; human, medical, veterinary, food, or household use. soluble in water at 8 mg/mL with warming; buffers, serum, • This product is offered for R&D use in accordance with (i) 35 or other additives may increase or decrease the aqueous USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese solubility. Disposal: A Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Ruxolitinib, also known as INCB18424, is a potent and selective Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Janus kinase JAK1 and JAK2 inhibitor, with IC50s of 2.7 and 4.5 nM, respectively. Verstovsek, S. et al., “INCB018424, an oral, and other common law exemptions of Canadian patent law; (vi) selective JAK2 inhibitor, shows significant clinical activity in a Section 68B of the Patents Act of 1953 in New Zealand together phase I/II study in patients with primary myelofibrosis (PMF) and with the amendment of same by the Statutes Amendment Bill of post polycythemia vera/essential thrombocythemia myelofibrosis 2002; (vii) such related legislation and/or case law as may be or (post-PV/ET MF).” Blood (ASH Annual Meeting Abstracts) become applicable in the aforementioned countries; and (viii) such 110: 558 (2007), see also http://www.incyte.com/ASH_ similar laws and rules as may apply in various other countries. Presentation_12.10.07.pdf. • Not available in some countries; not available to some institutions; • This product is the phosphate salt form of ruxolitinib. We not available for some uses. also offer the free base form; please see Ruxolitinib, Free CN Base (Cat. No. R‑6600 on page 100). The phosphate salt form of ruxolitinib is used for some or all ruxolitinib formulations for use in humans. N N O • Ruxolitinib suppressed interleukin-6 signaling (IC50 = 281 nM) H O POH and proliferation of JAK2V617F+ Ba/F3 cells (IC50 = 127 nM). In primary cell cultures, ruxolitinib more selectively inhibited N OH erythroid progenitor colony formation from JAK2V617F+ N polycythemia vera patients (IC50 = 67 nM) when compared N H to healthy donors (IC50 > 400 nM). In a mouse model of JAK2V617F+ myeloproliferative neoplasm, ruxolitinib significantly reduced splenomegaly and circulating levels of RWJ-540973 — see JNJ-10198409, Free Base inflammatory cytokines, selectively eliminated neoplastic cells, (Cat. No. J-4567 on page 59). and thus markedly prolonged survival without myelosuppressive SAHA — see Vorinostat (Cat. No. V-8477 on page 124). or immunosuppressive effects. Quintás-Cardama, A. et al., “Preclinical characterization of the selective JAK1/2 inhibitor S-9033 Salinomycin INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.” Blood 115: 3109‑3117 (2010). (Please inquire for availability or visit www.lclabs.com) • Ruxolitinib inhibited phosphorylated signal transducer and Salvin — see Carnosic Acid, Free Acid (Cat. No. C-2662 on page 18). activator of transcription 3 (STAT3) in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation. Ruxolitinib Sandimune — see its active ingredient, namely Cyclosporin A reduced the spleen size of the patients with myelofibrosis with (Cat. No. C-6000 on page 25). or without JAK2 V617F. It also rapidly improved symptoms, SAPK Inhibitor II — see SP600125 (Cat. No. S-7979 on page 107). including weight loss, fatigue, night sweats, and pruritus. Clinical improvements were associated with significantly reduced levels of circulating inflammatory cytokines. Verstovsek, S. et al., “Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.” N. Engl. J. Med. 363: 1117‑1127 (2010).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 101 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

in patients with advanced castration-resistant prostate cancer: a S-8906 Saracatinib, Free Base, >99% California Cancer Consortium study.” Anticancer Drugs [AZD 0530] 20: 179-184 (2009). • Sold for laboratory or manufacturing purposes only; not for Size US$ ¤ £ ¥ human, medical, veterinary, food, or household use. 10 mg 52 40 34 5,800 • This product is offered for R&D use in accordance with (i) 35 25 mg 93 72 61 10,400 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 50 mg 152 117 100 17,000 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 100 mg 247 191 163 27,600 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 200 mg 410 317 271 45,800 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 500 mg 562 434 372 62,800 and other common law exemptions of Canadian patent law; (vi) 1 g 933 721 617 104,300 Section 68B of the Patents Act of 1953 in New Zealand together 2 g 1620 1252 1071 181,100 with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. M.W. 542.03 c H ClN O [379231-04-6] 27 32 5 5 • Not available in some countries; not available to some institutions; Storage: Store at or below -20 ºC. not available for some uses. Solubility: Soluble in DMSO at 200 mg/mL; soluble in O N ethanol at 200 mg/mL; maximum solubility in plain water is N estimated to be about 20-100 µM; buffers, serum, or other N N additives may increase or decrease the aqueous solubility. Me O

Disposal: A O N O H • Saracatinib an orally available Src kinase inhibitor. O • Saracatinib inhibits c-Src and Abl enzymes at low nanomolar Cl concentrations. Saracatinib blocked the tumor growth of a c-Src-transfected 3T3-fibroblast xenograft in vivo and increased SB 95952 — see (R,S)-Rolipram (Cat. No. R-2020 on page 98). significantly the survival of animals in a highly aggressive model of human pancreatic cancer. Hennequin L.F. et al., “N-(5-chloro- S-1700 SB 202190, Free Base, >99% 1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- [FHPI] [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-S-8906-2009-10-17-kedREV.SKC (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, (4-pyridyl)1H-imidazole] highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor.” J. Med. Chem. 49: 6465-6488 (2006). Size US$ ¤ £ ¥ • Saracatinib blocked the proliferation of various cell lines tested 25 mg 32 25 21 3,600 (IC50 = 0.2 ->10 µM) and inhibited tumor growth in 4/10 xenograft 50 mg 46 36 30 5,100 models tested. Saracatinib had significant antimigratory and anti- 100 mg 89 69 59 10,000 invasive effects in vitro, and inhibited metastasis of bladder cancer 200 mg 169 131 112 18,900 in vivo. Saracatinib blocked phosphorylation of Src substrates 500 mg 375 290 248 41,900 paxillin and FAK in both growth-inhibition-resistant and -sensitive 1 g 620 479 410 69,300 xenografts. Green T.P. et al., “Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530.” Mol. Oncol. 2009 Feb 7. 2 g 1128 872 746 126,100 NOTE: Euro, Pound and Yen prices are revised regularly. • Saracatinib blocked the growth of, and induced apoptosis in, Please visit www.LCLabs.com for our current prices. chronic myeloid leukaemia (CML) and Ph+ acute lymphoblastic leukaemia (ALL) cells, but showed only slight effects on Ph- M.W. 331.34 c20H14FN3O [152121-30-7] ALL cells. Saracatinib overcame the resistance to imatinib due Storage: Store at or below -20 ºC. Solubility: Soluble in to the mutation Y253F in p185Bcr-Abl. Combination treatment DMSO. Disposal: A of saracatinib and imatinib showed an additive inhibitory effect • SB 202190, a pyridinyl imidazole, inhibits p38 on the proliferation of CML BV173 cells but not on Ph+ ALL kinase activity in vivo through competition with ATP. SupB15 cells. Gwanmesia P.M. et al., “The effect of the dual Src/ Young, P.R. et al., “Pyridinyl Imidazole Inhibitors of p38 Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia Mitogen-activated Protein Kinase Bind in the ATP Site.” cell lines.” BMC Cancer 9: 53 (2009). J. Biol. Chem. 272: 12116‑12121 (1997). • Saracatinib inhibited the anchorage-dependent growth of MCF-7 • Induces apoptosis through activation of cysteine protease (CPP32)- with IC50 of 0.47 µM, which was increased 4-fold in the presence like caspases . Nemoto, S. et al., “Induction of apoptosis by SB of estrogen. In contrast, saracatinib inhibited the growth of 202190 through inhibition of p38beta mitogen-activated protein cells stably expressing the mutant ERα with an elevated IC50 kinase.” J. Biol. Chem. 273: 16415-16420 (1998). that was only increased 1.4-fold by estrogen stimulation. The results indicated that c-Src inhibition is blocked by estrogen • Blocks both lipopolysaccharide (LPS)-induced gene expression signaling. Herynk M.H. et al., “Cooperative action of tamoxifen and nitric oxide (NO)-induced stabilization of interleukin (IL)- and c-Src inhibition in preventing the growth of estrogen 8 mRNA in monocytes. Manthey, C.L. et al., “SB 202190, a receptor-positive human breast cancer cells.” Mol. Cancer Ther. selective inhibitor of p38 mitogen-activated protein kinase, is 5: 3023‑3031 (2006). a powerful regulator of LPS-induced mRNAs in monocytes.” J. Leukoc. Biol. 64: 409-417 (1998). Ma, P. et al., “Nitric • Saracatinib inhibited the proliferation of DU145 and PC3 prostate oxide post-transcriptionally up-regulates LPS-induced IL-8 cancer cells, apparently by reducing binding of beta-catenin to expression through p38 MAPK activation.” J. Leukoc. Biol. the promoters of G1 phase cell cycle regulators cyclin D1 and 76: 278‑287 (2004). c-Myc. Saracatinib also decreased orthotopic DU145 xenograft growth by 45% in mice. Chang Y.M. et al., “Src family kinase • Sold for laboratory or manufacturing purposes only; not for oncogenic potential and pathways in prostate cancer as revealed by human, medical, veterinary, food, or household use. AZD0530.” Oncogene 27: 6365-6375 (2008). OH N • Saracatinib treatment is feasible and tolerable in previously treated N patients suffering from advanced castration-resistant prostate cancer, but it had little clinical efficacy as monotherapy. Lara P.N. N Jr. et al., “A phase II trial of the Src-kinase inhibitor AZD0530

F 102 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

neutrophil margination in vivo. White, J.R. et al., “Identification S-3400 SB 203580, Free Base, >99% of a potent, selective non-peptide CXCR2 antagonist [4-(4'‑Fluorophenyl)-2-(4'-methylsulfinylphenyl)-5- that inhibits interleukin-8-induced neutrophil migration.” (4'-pyridyl)imidazole] J. Biol. Chem. 273: 10095‑10098 (1998). • SB 225002 significantly inhibited replication of HIV-1BRU in Size US$ ¤ £ ¥ peripheral blood lymphocytes and of HIV-1BaL in monocyte- 25 mg 55 43 36 6,100 derived macrophages. Lane, B.R. et al., “Interleukin-8 50 mg 72 56 48 8,000 stimulates human immunodeficiency virus type 1 replication 100 mg 129 100 85 14,400 and is a potential new target for antiretroviral therapy.” 200 mg 228 176 151 25,500 J. Virol. 75: 8195‑8202 (2001). 500 mg 527 407 348 58,900 • SB 225002 indirectly inhibited gamma-secretase and reduced 1 g 845 653 559 94,500 amyloid β. It has the potential to be used to treat Alzheimer’s NOTE: Euro, Pound and Yen prices are revised regularly. disease. Bakshi, P. et al., “Structural optimization of a CXCR2- Please visit www.LCLabs.com for our current prices. directed antagonist that indirectly inhibits gamma-secretase and M.W. 377.43 C H FN OS [152121-47-6] reduces Abeta.” Bioorg. Med. Chem. 17: 8102‑8112 (2009). 21 16 3 • Growth-related oncogenes GROα, GROβ, and CXCR2 Storage: Store at or below -20 °C. were up-regulated in esophageal tumor tissue. SB 225002 Solubility: Soluble in DMSO at 100 mg/mL; soluble in intervened in GROα-CXCR2 and GROβ-CXCR2 signaling ethanol at 12.5 mg/mL with warming; very poorly soluble and inhibited esophageal tumorigenesis. Wang, B. et al., “A in water; maximum solubility in plain water is estimated to growth-related oncogene/CXC chemokine receptor 2 autocrine be about 10-50 µM; buffers, serum, or other additives may loop contributes to cellular proliferation in esophageal cancer.” increase or decrease the aqueous solubility. Appearance: white to off-white solid. Disposal: A Cancer Res. 66: 3071‑3077 (2006). • After infection with S. pneumoniae, SB 225002 inhibited alveolar • Important, highly specific new inhibitor of the kinase known neutrophil and exudate macrophage recruitment in mice and led variously as p38, p40, CSBP or RK. This kinase is a homolog to increased lung bacterial loads. Herbold, W. et al., “Importance of MAP kinase. Gallagher, T. F. et al., “2,4,5-Triarylimidazole of CXC chemokine receptor 2 in alveolar neutrophil and exudate inhibitors of Il-1 biosynthesis.” Bioorg. Med. Chem. Lett. macrophage recruitment in response to pneumococcal lung 5: 1171‑1176 (1995); Cuenda, A. et al., “SB203580 is infection.” Infect. Immun. 78: 2620‑2630 (2010). a specific inhibitor of MAP kinase homologue which is stimulated by cellular stresses and interleukin-1.” FEBS Lett. • SB 225002 had inhibitory effects on both acute and chronic 364: 229‑233 (1995); Hazzalin, C.A. et al., “Effects of the pain. Manjavachi, M.N. et al., “The effects of the selective inhibition of p38/RK MAP kinase on induction of five fos and jun and non-peptide CXCR2 receptor antagonist SB225002 genes by diverse stimuli.” Oncogene 15: 2321-2331 (1997). on acute and long-lasting models of nociception in mice.” Eur. J. Pain 14: 23‑31 (2010). • We note that one of our competitors, biorbyt.com, as of February 12, 2013, is claiming 99.9% purity for its SB 203580. This claim • SB 225002 ameliorated 2,4,6-trinitrobenzene sulfonic is not credible in general chemical terms for this complex organic acid-induced experimental colitis in mice. Bento, A.F. compound, nor in terms of the sensitivity and reproducibility of et al., “The selective nonpeptide CXCR2 antagonist generally utilized analytical techniques. SB225002 ameliorates acute experimental colitis in mice.” J. Leukoc. Biol. 84: 1213‑1221 (2008). • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. N • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent HN Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. N Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) F S and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together O with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or S-5100 SB 225002, >99% become applicable in the aforementioned countries; and (viii) such Size US$ ¤ £ ¥ similar laws and rules as may apply in various other countries. 5 mg 49 35 31 3,700 • Not available in some countries; not available to some institutions; not available for some uses. 10 mg 86 62 54 6,600 25 mg 198 142 124 15,100 Br H H OH 50 mg 345 248 216 26,300 N N 100 mg 550 396 345 42,000 O NO 300 mg 996 717 624 76,000 2 1 g 1975 1421 1238 150,700 NOTE: Euro, Pound and Yen prices are revised regularly. SC-58635 — see Celecoxib (Cat. No. C-1502 on page 20). Please visit www.LCLabs.com for our current prices. SDZ-ASM-981 — see Pimecrolimus (Cat. No. P-6040 on page 91). M.W. 352.14 c13H10BrN3O4 [182498-32-4] Storage: Store at or below -20 ºC. Solubility: Soluble in SDZ-RAD – see Everolimus (Cat. No. E-4040 on page 40). DMSO. Disposal: A Seliciclib – see Roscovitine (Cat. No. R-1234 on page 99). • SB 225002 is a potent and selective CXCR2 antagonist. It inhibited IL-8 binding to CXCR2 with an IC50 of 22 nM. SB 225002 showed >150-fold selectivity over CXCR1 and four other seven-transmembrane receptors tested. SB 225002 potently inhibited human and rabbit neutrophil chemotaxis induced by both IL-8 and GROα in vitro and IL-8-induced rabbit

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 103 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

the original tumors remained viable. Combination treatment of S-4490 Selumetinib, Free Base, >99% selumetinib with docetaxel caused tumor regression. Haass, N.K. Synonyms: [ARRY-886] [ARRY-142886] [AZD6244] et al., “The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth Size US$ ¤ £ ¥ arrest in melanoma cells and tumor regression when combined 100 mg 43 33 28 4,300 with docetaxel.” Clin. Cancer Res. 14: 230‑239 (2008). 200 mg 64 49 42 6,400 • Selumetinib inhibited the growth of a spectrum of thyroid 500 mg 118 90 77 11,700 cancer cells by inhibiting the MEK-ERK pathway. However, 1 g 211 162 139 21,000 the inhibitory effect was cytostatic in papillary thyroid cancer 2 g 390 299 256 38,800 and anaplastic thyroid cancer cells bearing a BRAF mutation. 5 g 935 716 614 93,000 Selumetinib may have less inhibitory impact on thyroid cancer cells lacking this mutation. Ball, D.W. et al., “Selective growth 10 g 1690 1294 1109 168,100 inhibition in BRAF mutant thyroid cancer by the mitogen- NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. activated protein kinase kinase 1/2 inhibitor AZD6244.” J. Clin. Endocrinol. Metab. 92: 4712‑4718 (2007). M.W. 457.68 C H BrClFN O [606143-52-6] 17 15 4 3 • Selumetinib induced myeloma-cell cytotoxicity and inhibited Storage: Store at or below -20 ºC. Solubility: Soluble in osteoclastogenesis, possibly by inhibiting MEK. Tai, Y.T. et al., DMSO at 200 mg/mL; soluble in ethanol at 2.5 mg/mL with “Targeting MEK induces myeloma-cell cytotoxicity and inhibits warming; very poorly soluble in water; maximum solubility osteoclastogenesis.” Blood 110: 1656‑1663 (2007). in plain water is estimated to be about 25-50 µM; buffers, • Related CAS numbers: 943332-08-9 for the selumetinib sulfate. serum, or other additives may increase or decrease the aqueous solubility. Disposal: A • Another CAS number previously assigned to Selumetinib, Free Base, namely 865610-79-3, has been deleted by CAS and is no • Selumetinib, also known as AZD6244, is a specific MEK1/2 longer in use. inhibitor with an IC50 value of 14 nM against purified MEK1. Yeh, T.C. et al., “Biological characterization of • Sold for laboratory or manufacturing purposes only; not for ARRY-142886 (AZD6244), a potent, highly selective human, veterinary, food, or household use. mitogen-activated protein kinase kinase 1/2 inhibitor.” • This product is offered for R&D use in accordance with (i) 35 Clin. Cancer Res. 13: 1576‑1583 (2007). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Selumetinib inhibited the growth of primary hepatocellular Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent carcinoma (HCC) cells in vitro and the growth of 7 HCC Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. xenografts dose-dependently in vivo, possibly by inactivating Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) ERK1/2 and p90RSK and up-regulating activated caspase-3, and other common law exemptions of Canadian patent law; (vi) caspase-7 and cleaved poly(ADP)ribose polymerase. Section 68B of the Patents Act of 1953 in New Zealand together Huynh, H. et al., “Targeted inhibition of the extracellular with the amendment of same by the Statutes Amendment Bill of signal-regulated kinase kinase pathway with AZD6244 2002; (vii) such related legislation and/or case law as may be or (ARRY-142886) in the treatment of hepatocellular carcinoma.” become applicable in the aforementioned countries; and (viii) such Mol. Cancer Ther. 6: 138‑146 (2007). similar laws and rules as may apply in various other countries. • The combination of selumetinib and MK2206 at ratios of 8:1, • Not available in some countries; not available to some institutions; 4:1, and 2:1 has a significant synergistic inhibitory effect on the not available for some uses. growth of human non-small cell lung cancer in vitro and in vivo H

and improves the survival of mice bearing highly aggressive HO N O human lung tumors. Meng, J. et al., “Combination treatment O H Cl with MEK and AKT inhibitors is more effective than each drug N alone in human non-small cell lung cancer in vitro and in vivo.” PLoS One 5: e14124 (2010). H C F Br • Selumetinib and the mTOR inhibitor rapamycin had synergistic 3 N N inhibitory effects on the growth of BxPC-3 and MIA PaCa-2 pancreatic cancers in vivo. Selumetinib also demonstrated a significant anti-angiogenic effect. Chang, Q. et al., “Effects of S-7272 Sepantronium Bromide, >98% combined inhibition of MEK and mTOR on downstream signaling Synonyms: [YM155] and tumor growth in pancreatic cancer xenograft models.” Cancer Biol. Ther. 8: 1893‑1901 (2009). Size US$ ¤ £ ¥ • When fractionated tumor-localized radiotherapy (5 x 2 Gy) was 5 mg 44 33 26 5,300 combined with selumetinib treatment, the growth delay of Calu-6 Prices 10 mg 68 51 41 8,200 lung and colorectal tumor xenografts was enhanced significantly Reduced! 25 mg 149 111 89 18,000 when compared with either treatment alone. Shannon, A.M. et al., 50 mg 270 201 161 32,500 “The mitogen-activated protein/extracellular signal-regulated 100 mg 440 328 262 53,000 kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances 200 mg 742 553 442 89,400 the radiation responsiveness of lung and colorectal tumor NOTE: Euro, Pound and Yen prices are revised regularly. xenografts.” Clin. Cancer Res. 15: 6619‑6629 (2009). Please visit www.LCLabs.com for our current prices. • The levels of phosphorylated AKT were significantly higher M.W. 443.29 c H BrN O [781661-94-7] in resistant lung cancer cells than in the sensitive cells. 20 19 4 3 Phosphorylated AKT can be used as a molecular biomarker Storage: Store at or below -20 ºC. Solubility: Soluble in to predict lung cancer response to MEK inhibitors. Meng, J. DMSO. Disposal: A et al., “High level of AKT activity is associated with • Sepantronium bromide, also known as YM155, is a novel small resistance to MEK inhibitor AZD6244 (ARRY-142886).” molecule inhibitor of expression of the survivin protein, which Cancer Biol. Ther. 8: 2073‑2080 (2009). itself is an inhibitor of apoptosis. • Selumetinib was cytostatic and inhibited the growth of melanoma • Sepantronium bromide inhibited the the growth of various human cells in vitro. In vivo, selumetinib treatment decreased phospho- cancer cell lines in vitro with GI50 values of 8.2 nM for null p53 ERK in the 1205Lu melanoma tumors and significantly suppressed PC-3, 2.3 nM for mutant p53 PPC-1, 4.0 nM for mutant p53 tumor growth in severe combined immunodeficient mice. But DU145, 8.2 nM for mutant p53 TSU-Prl, 11 nM for mutant p53 selumetinib monotherapy was largely only cytostatic because 22Rvl hormone refractory prostate cancer cells; 4.2 nM for wt p53

104 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

SK-MEL-5, and 6.3 nM for wt p53 A375 malignant melanoma. • A phase II clinical trial showed that sepantronium bromide had Sepantronium bromide also induced extensive regression of modest activity in taxane-pretreated castration-resistant prostate xenografted PC-3 tumors in mice. Nakahara, T. et al., “YM155, a cancer (CRPC) and was also well tolerated. Tolcher, A.W. et al., novel small-molecule survivin suppressant, induces regression of “A phase II study of YM155, a novel small-molecule suppressor of established human hormone-refractory prostate tumor xenografts.” survivin, in castration-resistant taxane-pretreated prostate cancer.” Cancer Res. 67: 8014‑8021 (2007). Ann. Oncol. (Aug 22, 2011 - Epub ahead of print). • Sepantronium bromide sensitized human non-small cell lung • Sold for laboratory or manufacturing purposes only; not for cancer (NSCLC) cells to γ-radiation both in vitro and in vivo. human, veterinary, food, or household use. Iwasa, T. et al., “Radiosensitizing effect of YM155, a novel small- • This product is offered for R&D use in accordance with (i) 35 molecule survivin suppressant, in non-small cell lung cancer cell USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese lines.” Clin. Cancer Res. 14: 6496‑6504 (2008). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • The uptake of [14C]sepantronium bromide into PC-3, lung Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. cancer (Calu-6 and NCI-H358), malignant melanoma (A375 and Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) SK-MEL-5), and non-Hodgkin’s lymphoma (RL and Ramos) and other common law exemptions of Canadian patent law; (vi) cell lines was dependent on incubation time, temperature, and Section 68B of the Patents Act of 1953 in New Zealand together drug concentration. Sepantronium bromide was taken up into with the amendment of same by the Statutes Amendment Bill of these different cancer cells in a carrier-mediated manner and with 2002; (vii) such related legislation and/or case law as may be or a similar affinity (Km = 0.189-0.367 µM). Minematsu, T. et al., become applicable in the aforementioned countries; and (viii) such “Carrier-mediated uptake of 1-(2-methoxyethyl)-2-methyl-4,9- similar laws and rules as may apply in various other countries. dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d] • Not available in some countries; not available to some institutions; imidazolium bromide (YM155 monobromide), a novel small- not available for some uses. molecule survivin suppressant, into human solid tumor and lymphoma cells.” Drug Metab. Dispos. 37: 619‑628 (2009). N • Sepantronium bromide blocked the growth of 119 human O N cancer cell lines, with the greatest inhibition in lines derived N + from non-Hodgkin’s lymphoma, hormone-refractory prostate Br - cancer, ovarian cancer, sarcoma, non-small-cell lung cancer, N OCH 3 breast cancer, leukemia and melanoma with an average GI50 of 15 nM. Sepantronium bromide inhibited the growth of tumor cell O lines regardless of their p53 status and demonstrated significant SILA 9268A – see Rapamycin (Cat. No. R-5000 on page 96). antitumor activity in 5 various mice xenograft models without showing significant bodyweight loss. It also caused tumor Sirolimus – see Rapamycin (Cat. No. R-5000 on page 96). regressions in vivo, possibly by its effects in reducing intratumoral SKI-606 – see Bosutinib, Free Base (Cat. No. B-1788 on page 12). survivin expression levels, increasing apoptosis and decreasing mitotic indices. Nakahara, T. et al., “Broad spectrum and potent SNDX 275 – see Entinostat, Free Base (Cat. No. E-3866 on page 34). antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and Solexa – see Celecoxib (Cat. No. C-1502 on page 20). xenograft models.” Cancer Sci. 102: 614‑621 (2011). S-8599 Sorafenib, Free Base • Sepantronium bromide demonstrated modest single-agent [Bay 43-9006] [Nexavar] activity in patients with refractory and advanced non-small- cell lung cancer (NSCLC) in a multicenter phase II trial. A Size US$ ¤ £ ¥ favorable safety/tolerability profile for sepantronium bromide was reported. Giaccone, G. et al., “Multicenter phase II trial of 300 mg 33 25 21 2,600 YM155, a small-molecule suppressor of survivin, in patients 500 mg 53 40 34 4,100 with advanced, refractory, non-small-cell lung cancer.” 1 g 86 65 55 6,700 J. Clin. Oncol. 27: 4481‑4486 (2009). 2 g 158 120 100 12,300 • Sepantronium bromide induced autophagy-dependent apoptosis 5 g 355 269 225 27,600 in prostate cancer cells. Wang, Q. et al., “Induction of autophagy- 10 g 680 515 431 52,800 dependent apoptosis by the survivin suppressant YM155 in 25 g 1625 1231 1031 126,200 prostate cancer cells.” Cancer Lett. 302: 29‑36 (2011). NOTE: Euro, Pound and Yen prices are revised regularly. • Sepantronium bromide induced spontaneous apoptosis of Please visit www.LCLabs.com for our current prices. melanoma cells, possibly by inhibiting survivin. It also M.W. 464.82 c21H16ClF3N4O3 [284461-73-0] demonstrated antiproliferative effects at nanomolar levels and Storage: Store at or below -20 °C. Solubility: Soluble in caused tumor regression in established melanoma xenograft DMSO at 200 mg/mL; soluble in ethanol at 3.3 mg/mL with models. Yamanaka, K. et al., “Antitumor Activity of YM155, a warming; very poorly soluble in water; maximum solubility Selective Small-Molecule Survivin Suppressant, Alone and in in plain water is estimated to be about 10-50 µM; buffers, Combination with Docetaxel in Human Malignant Melanoma serum, or other additives may increase or decrease the Models.” Clin. Cancer Res. 17: 5423‑5431 (2011). aqueous solubility. Disposal: A • Sepantronium bromide induced decreased cellular proliferation • This is the free base form of sorafenib. See Sorafenib, and spontaneous apoptosis of human metastatic triple negative p-Toluenesulfonate Salt (Cat. No. S-8502 on page 106) for further breast cancer cells (TNBC, with negative expression of estrogen technical information. It is the p-toluenesulfonate salt form, not and progesterone receptors and no overexpression of HER2/ the free base, that is used in the formulation of sorafenib for in neu (ErbB-2)). In a preclinical TNBC mouse xenograft model, vivo use. continuous treatment with sepantronium bromide caused the complete regression of subcutaneously established tumors. This • Sorafenib is the active ingredient in the drug sold under the trade ® compound inhibited spontaneous metastases and significantly name Nexavar . The drug is curently approved in at least one improved the survival of animals bearing established metastatic country for use in patients with advanced renal cell cancer. NOTE: ® tumors. Yamanaka, K. et al., “YM155, a selective survivin the sorafenib sold by LC Laboratories is NOT Nexavar and is suppressant, inhibits tumor spread and prolongs survival in a NOT for human use. spontaneous metastatic model of human triple negative breast • Sold for laboratory or manufacturing purposes only; not for cancer.” Int. J. Oncol. 39: 569‑575 (2011). human, medical, veterinary, food, or household use.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 105 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• This product is offered for R&D use in accordance with (i) 35 V599E BRAF mutant 38 ± 9 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent VEGFR-2 90 ± 15 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) mVEGFR-2 (flk-ss1) 15 ± 6 and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together mVEGR-3 20 ± 6 with the amendment of same by the Statutes Amendment Bill of mPDGFR-β 57 ± 20 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such Flt-3 58 ± 20 similar laws and rules as may apply in various other countries. c-KIT 68 ± 21 • Not available in some countries; not available to some institutions; not available for some uses. FGFR-1 580 ± 100

CF O 3 ERK-1, MEK-1, EGFR, HER-2, IGFR-1, Cl O c-met, PKB, PKA, cdk1/cyclinB, PKC, PKC, >10,000 O N pim-1 N H NN Cellular Mechanism HH MDA MB 231 MEK phosphorylation 40 ± 20 S-8502 Sorafenib, p-Toluenesulfonate Salt, >99% (human breast) [Bay 43-9006] [Nexavar] [Sorafenib Tosylate] MDA MB 231 ERK 1/2 phosphorylation 90 ± 26 (human breast) Size US$ ¤ £ ¥ 300 mg 33 25 21 2,600 BxPC-3 ERK 1/2 phosphorylation 1,200 ± 165 500 mg 53 40 34 4,100 (human pancreatic) S-8599-2008-11-15-kedRev.SKC1 g 86 65 55 6,700 LOX ERK 1/2 phosphorylation 880 ± 90 2 g 158 120 100 12,300 (human melanoma) 5 g 355 269 225 27,600 VEGFR-2 phosphorylation 10 g 680 515 431 52,800 30 ± 21 25 g 1625 1231 1031 126,200 (human, NIH 3T3 cells) NOTE: Euro, Pound and Yen prices are revised regularly. VEGF-ERK 1/2 phosphorylation Please visit www.LCLabs.com for our current prices. 60 ± 26 (human, HUVEC) M.W. 637.03 C21H16ClF3N4O3 •C7H8O3S [475207-59-1] M.I. 14: 8720 PDGFR-β phosphorylation (human HAoSMC) 80 ± 40 Storage: Store at or below -20 °C. Solubility: Soluble mVEGFR-3 phosphorylation 100 ± 80 in DMSO at 200 mg/mL; very poorly soluble in ethanol; (mouse, HEK-293 cells) very poorly soluble in water; maximum solubility in plain Flt-3 phosphorylation water is estimated to be about 10-20 µM; buffers, serum, 20 ± 10 or other additives may increase or decrease the aqueous (human ITD, HEK-293 cells) solubility. Disposal: A Cellular Proliferation • Sorafenib (Bay 43-9006) is a novel bi-aryl urea compound that inhibits cell proliferation by targeting the ERK pathway and MDA MB 231 (10% FCS) 2,600 ± 810 angiogenesis by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR-β and their associated signaling cascades. Although PDGF-BB HAoSMC 280 ± 140 sorafenib was initially developed as a Raf kinase inhibitor (IC50 = 6 nM), it has since been shown to have activity against * Kinase assays were carried out at ATP concentrations at or many receptor tyrosine kinases involved in tumorigenesis and below Km (1-10 µM) angiogenesis including FGFR-1, wt BRAF and V599E mutant ** Lck-activated NH2-terminal-truncated Raf-1 BRAF, as well as members of the so-called “split kinase” • Sorafenib is more potent in a cellular system (IC = 20 nM) family: VEGFR-2, VEGFR-3, PDGFR-β, c-KIT, and Flt3. 50 than in an enzyme assay (IC = 107 nM). Guo, J. et al., However, sorafenib is not active against erbB1, erbB2, ERK-1, 50 MEK-1, EGFR, HER-2, IGFR-1, c-MET, c-yes, PKB, PKA, “Inhibition of phosphorylation of the colony-stimulating cdk1/cyclinB, PKC, and pim-1. In cellular mechanistic assays, factor-1 receptor (c-Fms) tyrosine kinase in transfected sorafenib decreased basal phosphorylation of the ERK pathway cells by ABT-869 and other tyrosine kinase inhibitors.” in melanoma, breast, colon, and pancreatic tumor cell lines. Mol. Cancer Ther. 5: 1007‑1013 (2006). Wilhelm, S.M. et al., “BAY 43-9006 Exhibits Broad Spectrum • Sorafenib potently inhibited activation of the MAPK pathway Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and ERK phosphorylation in human cancer cell lines, irrespective and Receptor Tyrosine Kinases Involved in Tumor Progression and of whether they harbored K-ras mutations, V599EB-Raf, or Angiogenesis.” Cancer Res. 64: 7099‑7109 (2004). both. Wilhelm, S. et al., “The novel Raf inhibitor Bay 43- • BAY 43-9006 inhibits the RAF/MEK/ERK pathway and receptor 9006 blocks signaling and proliferation in BRAF mutant tyrosine kinases involved in tumor angiogenesis (adapted from and wildtype melanoma and colorectal tumor cell lines.” Wilhelm, S.M. et al., 2004): Proc. Am. Assoc. Cancer Res. 44: 106609 (2003). • Sorafenib inhibited various nonkinase targets, including adenosine A3, dopamine D1, and muscarine M3 receptors, albeit at IC (nM) Biochemical Assay * 50 much higher (micromolar) concentrations than kinase targets. ± SD Carter, C. et al., “Investigators Brochure Bay 43-9006/Raf Kinase Inhibitor.” Version No. 5. West Haven, CT, Bayer Pharmaceuticals Raf-1 ** 6 ± 3 Corporation, 2004. BRAF wild-type 22 ± 6 • Sorafenib tosylate is the active ingredient in the drug sold under the trade name Nexavar®. This drug has been approved in at least

106 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

one country for use in patients with advanced renal cell cancer. JNK2 0.11 NOTE: The sorafenib tosylate sold by LC Laboratories is NOT Nexavar®, and is NOT for human use. JNK3 0.15 • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. ERK2 > 30 • This product is offered for R&D use in accordance with (i) 35 p38β > 30 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent IkB kinase-2 > 30 Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Acetylcholine esterase > 10 and other common law exemptions of Canadian patent law; (vi) Cycloxygenase-2 > 10 Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 5'-lipoxygenase > 10 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such PDE I, III, IV, V > 10 similar laws and rules as may apply in various other countries. iNOS > 10 • Not available in some countries; not available to some institutions; not available for some uses. Phospholipase A2 > 10

CF . C H O S O Adenylate cyclase > 10 3 7 8 3 Cl O O NH Guanylate cyclase > 10 N NH NH ATPase (Na/K) > 10

Sorafenib Tosylate – see Sorafenib, p-Toluenesulfonate Salt Protein kinase C > 10 (Cat. No. S-8502 on page 106). HIV-1 protease > 10 S-7979 SP600125, >99% Monoamine oxidase > 10 [Anthra(1,9-cd)pyrazol-6(2H)-one] [Anthrapyrazolone] [1,9-Pyrazoloanthrone] Tyrosine hydrolase > 10 [JNK Inhibitor II] [SAPK Inhibitor II] Elastase > 10 Size US$ ¤ £ ¥ Cathepsin B, G > 10 50 mg 48 39 31 3,800 EGFR tyrosine kinase > 10 100 mg 86 66 54 7,000 300 mg 135 103 85 11,000 500 mg 186 142 117 15,200 • SP600125 inhibited JNK, reduced the levels of c-Jun 1 g 334 255 210 27,300 phosphorylation, prevented apoptosis in dopaminergic neurons, 2 g 495 378 312 40,400 and partly reversed the loss of dopamine in MPTP-induced Parkinson’s disease in C57BL/6N mice. Wang, W. et al., NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. “SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson’s disease.” M.W. 220.23 c14H8N2O [129-56-6] Neurosci. Res. 48: 195‑202 (2004). Storage: Store at or below -20 °C. Solubility: Prepare • Sold for laboratory or manufacturing purposes only; not for initial stock solutions in DMSO (soluble at 200 mg/mL) for human, medical, veterinary, food, or household use. in vitro use; solubility in ethanol or water is low. Disposal: A N NH • Novel, potent and selective JNK-1,-2, and -3 inhibitor (Ki = 0.19 µM). SP600125 is an ATP-competitive reversible inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 caused a dose-dependent O inhibition of the phosphorylation of c-Jun, the expression Sprycel – see its active ingredient, namely Dasatinib of inflammatory genes IL-2, COX-2, TNF-α, IFN-γ, and (Cat. No. D-3307 on page 27). blocked the activation and differentiation of primary human CD4 cell cultures. In animal studies, SP600125 inhibited SR-11247 – see Bexarotene (Cat. No. B-2422 on page 10). bacterial lipopolysaccharide-induced expression of tumor SR1 – see StemRegenin 1, Free Base (Cat. No. S-2440 on page 109). necrosis factor-α and prevented anti-CD3-induced apoptosis of CD4+ CD8+ thymocytes. Bennett, B.L. et al., “SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.” Proc. Natl. Acad. Sci. USA 98: 13681‑13686 (2001). • SP600125 completely inhibited IL-1-induced accumulation of phospho-Jun and initiation of c-Jun transcription in synoviocytes. Han, Z. et al., “c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis.” J. Clin. Invest. 108: 73‑81 (2001). • Inhibitory activity of SP600125 on various enzymes (adapted from Han, Z. et al.):

Enzyme IC50 (µM) JNK1 0.11

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 107 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

S-9344 Stauprimide, >99% S-9300 Staurosporine, Free Base, >99% [N-Benzoyl-7-oxostaurosporine] [Antibiotic AM-2282] [CGP 39360]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 1 mg 85 59 52 6,700 1 mg 47 36 31 5,300 5 mg 380 266 232 29,800 5 mg 116 90 77 13,000 10 mg 625 437 381 49,000 10 mg 167 129 110 18,700 25 mg 1275 891 777 100,000 25 mg 282 218 186 31,500 100 mg 2550 1783 1555 200,100 50 mg 497 384 329 55,600 NOTE: Euro, Pound and Yen prices are revised regularly. 100 mg 838 648 554 93,700 Please visit www.LCLabs.com for our current prices. 200 mg 1270 982 840 142,000 M.W. 584.62 c35H28N4O5 [154589-96-5] 300 mg 1525 1179 1008 170,500 Storage: Store at or below -20 °C. Solubility: Soluble in NOTE: Euro, Pound and Yen prices are revised regularly. DMSO at 100 mg/mL; very poorly soluble in ethanol; very Please visit www.LCLabs.com for our current prices. poorly soluble in water; maximum solubility in plain water M.W. 466.53 c28H26N4O3 [62996-74-1] is estimated to be about 1-10 µM; buffers, serum, or other M.I. 14: 8802 additives may increase or decrease the aqueous solubility. Disposal: A Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 100 mg/mL; soluble in ethanol at 2.5 mg/mL with • Stauprimide increases the efficiency of directed differentiation warming; very poorly soluble in water; maximum solubility of mouse and human embryonic stem cells (ESCs). Stauprimide in plain water is estimated to be about 10-20 µM; buffers, binds to NME2 and inhibits its nuclear localization, thus leading to serum, or other additives may increase or decrease the downregulation of c-Myc. Zhu S. et al., “A small molecule primes aqueous solubility. Disposal: A embryonic stem cells for differentiation.” Cell Stem Cell • CHECK THE PRICES! 4: 416-426 (2009). SIGMA – 1 mg – $873 • Stauprimide interacts with NME2, a c-Myc-activating transcription factor that is highly expressed in ESCs. Stauprimide treatment Calbiochem – 1 mg – $599 inhibits the nuclear localization of NME2 and downregulates Fisher BioReagents – 1 mg – $1169 c-Myc, enhances ESC exit from the pluripotent state and enables • SMART: Buy just 1 mg of staurosporine from LC Labs differentiation. Zaret K., “Using Small Molecules to Great Effect instead of Sigma; with the money you save, you can in Stem Cell Differentiation.” Cell Stem Cell 4: 373-374 (2009). buy a nice pH meter or about 40,000 pipet tips! • Sold for laboratory or manufacturing purposes only; not for • SMARTER: Buy 100-300 mg from LC Labs; support a postdoc human, medical, veterinary, food, or household use. for 1-2 years with the money you save! H • Staurosporine is a potent inhibitor of many, many kinases N including protein kinase C (IC = 0.7 nM), protein kinase A O O 50 (IC50 = 7 nM), protein kinase G (IC50 = 8.5 nM), and other kinases at sub-nanomolar potencies. Staurosprine is NOT a selective inhibitor of PKC, contrary to widespread erroneous citations in the literature. Matsumoto, H. et al., “Staurosporine, a protein N N kinase C inhibitor, interferes with proliferation of arterial smooth O muscle cells.” Biochem. Biophys. Res. Commun. 158: 105-109 H C H 3 S-9344 (1989). Tamaoki, T. et al., “Staurosporine, a potent inhibitor of H C O ++ 3 phospholipid/Ca dependent protein kinase.” Biochem. Biophys. Res. Commun. 135: 397-402 (1986). O N CH 3 • Staurosporine induces apoptosis in human neuroblastoma cell lines S-9344 2010-02-12 HZ_RevSKC.skc and chick embryonic neurons. Boix, J. et al., “Characterization of the cell death process induced by staurosporine in human neuroblastoma cell lines.” Neuropharmacology 36: 811-821 (1997). Wiesner, D.A. and Dawson, G., “Staurosporine induces programmed cell death in embryonic neurons and activation of the ceramide pathway.” J. Neurochem. 66: 1418-1425 (1996). • Please request Technical Note #24 for additional information. • We don’t want to waste much ink disparaging our competitors, but we can’t help noting that many vendors sell staurosporine, at purities lower than ours, for audacious prices of $300-600 per mg (!). • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.

NH O

N N O H C H 3 CH O 3 NHCH 3

Staurosporine Aglycone – see K-252c (Cat. No. K-9609 on page 60).

108 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

S-2440 StemRegenin 1, Free Base, >99% Suberoylanilide Hydroxamic Acid – see Vorinostat Synonyms: [SR1] (Cat. No. V-8477 on page 124). S-8877 Sunitinib, Free Base, >99% Size US$ ¤ £ ¥ [PHA-290940AD] [PNU-290940AD] [SU-11248] 10 mg 53 39 32 7,500 [Sutent] Prices 25 mg 112 82 68 15,800 Reduced! 50 mg 181 132 110 25,600 Size US$ ¤ £ ¥ 100 mg 319 233 194 45,100 300 mg 52 40 34 5,800 200 mg 522 382 317 73,800 500 mg 69 53 46 7,700 500 mg 1098 803 666 155,100 1 g 84 65 56 9,400 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 2 g 146 113 97 16,300 5 g 329 254 218 36,800 M.W. 429.54 c H N OS [1227633-49-9] 24 23 5 10 g 580 448 383 64,800 Storage: Store at or below -20 ºC. Solubility: Soluble in NOTE: Euro, Pound and Yen prices are revised regularly. DMSO. Disposal: A Please visit www.LCLabs.com for our current prices.

• StemRegenin 1 (SR1) is a purine derivative that promoted M.W. 398.47 C22H27FN4O2 [557795-19-4] + ex vivo expansion of CD34 cells, with an EC50 of ~120 nM M.I. 14: 9000 after treatment for 5 to 7 days. It induced a 17-fold increase in cells capable of long-term hematopoietic repopulation when Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 40 mg/mL; soluble in ethanol at 1.4 mg/mL; transplanted into immunodeficient mice. SR1 did not induce very poorly soluble in water; maximum solubility in plain proliferation without cytokines, and inhibited proliferation at water is estimated to be about 10-20 µM; buffers, serum, concentrations above 1 µM. SR1 expanded CD34+ cells from or other additives may increase or decrease the aqueous bone marrow of humans, monkeys and dogs, but not mice. SR1 solubility. Disposal: A promoted the retention of CD34 expression and multilineage potential after ex vivo culture. It also expanded the number of • This is the free base form of sunitinib; please see our product colony-forming units. SR1 may act by antagonizing the aryl Sunitinib, Malate Salt (Cat. No. S-8803 on page 110) for further hydrocarbon receptor. Boitano, A.E. et al., “Aryl hydrocarbon technical information. The malate salt form of sunitinib, not the receptor antagonists promote the expansion of human free base, is used in the sunitinib formulation for use in humans. hematopoietic stem cells.” Science 329: 1345‑1348 (2010). • Sunitinib (as the malate salt) is the active ingredient in the drug • Discovery of SR1 is a significant step towards the goal of sold under the trade name Sutent®. This drug is a small molecule ex vivo expansion of human hematopoietic stem cells (HSC) receptor tyrosine kinase inhibitor that is approved in at least for patients in need of HSC transplantation. Sauvageau, G. one country for the treatment of patients having gastrointestinal and Humphries, R.K., “The blood stem cell Holy Grail?” stromal tumors or renal cell carcinomas. NOTE: the sunitinib (as Science 329: 1291‑1292 (2010). the malate salt) sold by LC Laboratories is NOT Sutent® and is • Sold for laboratory or manufacturing purposes only; not for NOT for human use. human, veterinary, food, or household use. • Sold for laboratory or manufacturing purposes only; not for • This product is offered for R&D use in accordance with (i) 35 human, medical, veterinary, food, or household use. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • This product is offered for R&D use in accordance with (i) 35 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. and other common law exemptions of Canadian patent law; (vi) Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Section 68B of the Patents Act of 1953 in New Zealand together and other common law exemptions of Canadian patent law; (vi) with the amendment of same by the Statutes Amendment Bill of Section 68B of the Patents Act of 1953 in New Zealand together 2002; (vii) such related legislation and/or case law as may be or with the amendment of same by the Statutes Amendment Bill of become applicable in the aforementioned countries; and (viii) such 2002; (vii) such related legislation and/or case law as may be or similar laws and rules as may apply in various other countries. become applicable in the aforementioned countries; and (viii) such • Not available in some countries; not available to some institutions; similar laws and rules as may apply in various other countries. not available for some uses. • Not available in some countries; not available to some institutions; not available for some uses. OH

O

N NH H N N F N N O NH N N S CH 3 H C 3

STI-571 – see Imatinib, Free Base (Cat. No. I-5577 on page 53) and Imatinib, Methanesulfonate Salt (Cat. No. I-5508 on page 54). SU-11248 – see Sunitinib, Malate Salt (Cat. No. S-8803 on page 110) and Sunitinib, Free Base (Cat. No. S-8877 on page 109). Suberanilohydroxamic Acid – see Vorinostat (Cat. No. V-8477 on page 124).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 109 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Not available in some countries; not available to some institutions; S-8803 Sunitinib, Malate Salt, >99% not available for some uses. [PHA-290940AD] [PNU-290940AD] [SU-11248] [Sunitinib Maleate] [Sutent]

Size US$ ¤ £ ¥ 300 mg 52 40 34 5,800 500 mg 69 53 46 7,700 1 g 84 65 56 9,400 2 g 146 113 97 16,300 5 g 329 254 218 36,800 Sunitinib Maleate – see Sunitinib, Malate Salt (Cat. No. S-8803 on page 110). 10 g 580 448 383 64,800 NOTE: Euro, Pound and Yen prices are revised regularly. Sutent – see its active ingredient, namely Sunitinib, Malate Salt Please visit www.LCLabs.com for our current prices. (Cat. No. S-8803 on page 110) and Sunitinib, Free Base (Cat. No. S-8877 on page 109). M.W. 532.56 c22H27FN4O2 •C4H6O5 [341031-54-7] M.I. 14: 9000 Tacedinaline – see CI-994, Free Base (Cat. No. C-2606 on page 21). Storage: Store at or below -20 °C. Solubility: Soluble in Tacrolimus – see FK-506 (Cat. No. F-4900 on page 42). DMSO at 40 mg/mL; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water TAK-165 – see Mubritinib, Free Base (Cat. No. M-5602 on page 71). is estimated to be about 10-50 µM; buffers, serum or other additives may increase or decrease the aqueous solubility. T-7802 Tandutinib, Free Base, >99% Disposal: A [CT53518] [MLN518] • Sunitinib and its active metabolite (SU012662) are selective inhibitors of multiple receptor tyrosine kinases, including Size US$ ¤ £ ¥ platelet-derived growth factor receptor and vascular endothelial 25 mg 36 27 23 3,300 growth factor receptor, that are associated with tumor growth and 50 mg 55 41 35 5,100 angiogenesis. Deeks E.D. and Keating G.M., “Sunitinib.” Drugs 100 mg 92 69 58 8,500 66: 2255-2266 (2006). 200 mg 166 124 105 15,400 • Sunitinib is a potent inhibitor of colony-stimulating factor -1 500 mg 298 223 189 27,600

receptor kinase in an enzyme assay (IC50 = 7 nM) and inhibits 1 g 486 364 308 45,100

receptor phosphorylation in a cellular assay (IC50 = 61 nM). Guo NOTE: Euro, Pound and Yen prices are revised regularly. J. et al., “Inhibition of phosphorylation of the colony-stimulating Please visit www.LCLabs.com for our current prices. factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by M.W. 562.70 C H N O [387867-13-2] ABT-869 and other tyrosine kinase inhibitors.” Mol. Cancer Ther. 31 42 6 4 5: 1007-1013 (2006). Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol • Sunitinib reduced stem cell factor (SCF)-induced phosphotyrosine at 25 mg/mL with warming; very poorly soluble in water; levels on KIT in a dose-dependent manner, with an IC50 value maximum solubility in plain water is estimated to be between 1 and 10 nM. Sunitinib also inhibited SCF-stimulated about 50-100 µM; buffers, serum, or other additives may ERK1/2 phosphorylation in a dose-dependent manner, with an IC 50 increase or decrease the aqueous solubility. Disposal: A value consistent with that for inhibition of KIT phosphotyrosine levels. Sunitinib also inhibited SCF-stimulated proliferation in • Tandutinib (also known as MLN518 or CT53518) is an orally active inhibitor of Fms-like tyrosine kinase 3 (FLT3) kinase, NCI-H526 cells with an IC50 value of 2 nM. Abrams T.J. et al., “SU11248 Inhibits KIT and Platelet-derived Growth Factor PDGFRβ and c-Kit. It inhibits FLT3 phosphorylation, downstream Receptor ß in Preclinical Models of Human Small Cell Lung signaling and tumor growth in vitro and in animal models. Cheng, Cancer.” Mol. Cancer Ther. 2: 471-478 (2003). Y. and Paz, K., “Tandutinib, an oral, small-molecule inhibitor of • Sunitinib inhibited FLT3-ITD phosphorylation in a dose- FLT3 for the treatment of AML and other cancer indications.” IDrugs 11: 46-56 (2008). dependent manner with an IC50 of 50 nM following a 2-hour treatment. For the FLT3-ITD cell line MV-4-11, sunitinib • The sensitivity of cell lines to tandutinib is increased by FLT3 dramatically inhibited cellular proliferation in a dose-dependent siRNA-induced down-regulation of FLT3. Walters, D.K. et al., “RNAi-induced down-regulation of FLT3 expression in AML cell manner with an IC50 of 1 to 10 nM. O’Farrell A. et al., “SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in lines increases sensitivity to MLN518.” Blood 105: 2952-2954 vitro and in vivo.” Blood 101: 3597-3605 (2003). (2005). • Sunitinib is the active ingredient in the drug sold under the trade • In human FLT3-ITD-positive acute myelogenous leukemia (AML) name Sutent®. This drug is a small molecule receptor tyrosine cell lines, tandutinib induced apoptosis and inhibited FLT3-ITD kinase inhibitor that is approved in at least one country for the phosphorylation, cellular proliferation, and signaling through the treatment of patients having gastrointestinal stromal tumors MAP kinase and PI3 kinase pathways. In Ba/F3 cells expressing (GIST) or renal cell carcinoma (RCC). NOTE: the sunitinib sold different FLT3-ITD mutants, tandutinib also demonstrated by LC Laboratories is NOT Sutent® and is NOT for human use. inhibition of IL-3-independent cell growth and FLT3-ITD autophosphorylation, with an IC of 10-100 nM. Tandutinib was a • Sold for laboratory or manufacturing purposes only; not for 50 human, medical, veterinary, food, or household use. potent inhibitor of FLT3-ITD-induced disease in a murine model. Kelly, L.M. et al., “CT53518, a novel selective FLT3 antagonist • This product is offered for R&D use in accordance with (i) 35 for the treatment of acute myelogenous leukemia (AML).” Cancer USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Cell 1: 421-432 (2002). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Tandutinib inhibits the growth of blast colonies from FLT3 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) ITD-positive patients with acute myelocytic leukemia (AML) and other common law exemptions of Canadian patent law; (vi) more effectively than for blast colonies from ITD-negative AML Section 68B of the Patents Act of 1953 in New Zealand together patients, at concentrations that do not significantly block colony with the amendment of same by the Statutes Amendment Bill of formation of normal human progenitor cells. Tandutinib has 2002; (vii) such related legislation and/or case law as may be or moderate toxicity toward normal hematopoiesis at concentrations become applicable in the aforementioned countries; and (viii) such that are used in treating FLT3 ITD-positive leukemia in mice. similar laws and rules as may apply in various other countries. Griswold, I.J. et al., “Effects of MLN518, a dual FLT3 and KIT

110 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

inhibitor, on normal and malignant hematopoiesis.” Blood 104: 2912-2918 (2004). T-8040 Temsirolimus, >99% • Tandutinib inhibited FLT3 autophosphorylation and [CCI-779] [Torisel] phosphorylation of STAT5 and ERK in FLT3-ITD-transformed Ba/ Size US$ ¤ £ ¥ F3 cells (IC = 500 nM). However, there was a broad spectrum of 50 10 mg 47 36 31 5,300 sensitivity among the 8 activation loop mutants (IC50 = 500 nM - 10 µM) for the inhibition of phosphorylation of FLT3, STAT5, and 25 mg 107 83 71 12,000 ERK. The relative cellular sensitivity of the mutants to tandutinib 50 mg 191 148 126 21,400 for proliferation of FLT3-transformed Ba/F3 cells correlated with 100 mg 342 264 226 38,200 IC50s in the biochemical assays, indicating that certain activation 200 mg 535 414 354 59,800 loop mutations in FLT3 confer resistance to tandutinib. Clark, J.J. 300 mg 765 591 506 85,500 et al., “Variable sensitivity of FLT3 activation loop mutations to 500 mg 1172 906 775 131,000 the small molecule tyrosine kinase inhibitor MLN518.” Blood 104: 2867-2872 (2004). 1 g 1790 1384 1183 200,100 NOTE: Euro, Pound and Yen prices are revised regularly. • Sold for laboratory or manufacturing purposes only; not for Please visit www.LCLabs.com for our current prices. human, medical, veterinary, food, or household use. M.W. 1030.29 c56H87NO16 [162635-04-3] • This product is offered for R&D use in accordance with (i) 35 M.I. 14: 9142 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Storage: Store at or below -20 ºC. Solubility: Soluble in Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. DMSO at 200 mg/mL; soluble in ethanol at 200 mg/mL; Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) very poorly soluble in water; maximum solubility in plain and other common law exemptions of Canadian patent law; (vi) water is estimated to be about 10-20 µM; buffers, serum, Section 68B of the Patents Act of 1953 in New Zealand together or other additives may increase or decrease the aqueous with the amendment of same by the Statutes Amendment Bill of solubility. Disposal: A 2002; (vii) such related legislation and/or case law as may be or • Temsirolimus, a rapamycin (sirolimus) derivative, also known as become applicable in the aforementioned countries; and (viii) such CCI-779, is an mTOR inhibitor with anti-cancer activity. Wan, X. similar laws and rules as may apply in various other countries. et al., “CCI-779 Inhibits Rhabdomyosarcoma Xenograft Growth • Not available in some countries; not available to some institutions; by an Antiangiogenic Mechanism Linked to the Targeting of not available for some uses. mTOR/Hif-1α/VEGF Signaling.” Neoplasia 8: 394-401 (2006). • Antiangiogenic effects may contribute to the antitumor activity N N of temsirolimus observed in breast cancer. Del Bufalo, D. et al., “Antiangiogenic potential of the Mammalian target of rapamycin N inhibitor temsirolimus.” Cancer Res. 66: 5549-5554 (2006). N NH N O • Temsirolimus showed synergistic in vivo antimyeloma effects in combination with dexamethasone in a xenograft model. Yan, H. O O O et al., “Mechanism by Which Mammalian Target of Rapamycin Inhibitors Sensitize Multiple Myeloma Cells to Dexamethasone- Tanespimycin – see 17-AAG (Cat. No. A-6880 on page 1). Induced Apoptosis.” Cancer Res. 66: 2305-2313 (2006). Tarceva — see its active ingredient, namely Erlotinib, Free Base • In lymphoblasts from adult patients with acute lymphoblastic (Cat. No. E-4997 on page 37) and Erlotinib, Hydrochloride Salt leukemia (ALL), cells treated with sirolimus showed an increase (Cat. No. E-4007 on page 38). in apoptotic cells and a dramatic decrease in cell proliferation compared to untreated cells. Mice bearing NOD/SCID xenografts Targretin — see its active ingredient, namely Bexarotene treated with temsirolimus showed a decrease in splenomegaly (Cat. No. B-2422 on page 10). and in peripheral-blood blasts. On the other hand, untreated mice Targretyn — see Bexarotene (Cat. No. B-2422 on page 10). continued to show expansion of human ALL. Temsirolimus also down-regulated the mTOR signaling intermediate phospho-S6 Targrexin — see Bexarotene (Cat. No. B-2422 on page 10). in xenografted human ALL. Teachey, D.T. et al., “The mTOR Tasigna — see its active ingredient, namely Nilotinib inhibitor CCI-779 induces apoptosis and inhibits growth in (Cat. No. N-8207 on page 72). preclinical models of primary adult human ALL.” Blood 107: 1149-1155 (2006). Tasocitinib — see Tofacitinib, Free Base (Cat. No. T-1377 on page 114) • Temsirolimus is able to reverse cisplatin resistance in small cell and Tofacitinib, Citrate Salt (Cat. No. T-1399 on page 115). lung cancer cell lines selected for cisplatin resistance and in cell Taxoid XRP6258 — see Cabazitaxel (Cat. No. C-2581 on page 15). lines derived from patients who failed cisplatin therapy. Wu, C. et al., “Overcoming cisplatin resistance by mTOR inhibitor in lung Taxol — see its active ingredient, namely Paclitaxel cancer.” Mol. Cancer 4: 25-34 (2005). (Cat. No. P-9600 on page 80). • Temsirolimus is the active ingredient in the drug sold under the ® Taxotere — see its active ingredient, namely Docetaxel trade name Torisel . The drug is currently approved in at least (Cat. No. D-1000 on page 29). one country for use in patients with advanced renal (kidney) cell carcinoma. NOTE: the temsirolimus sold by LC Laboratories is NOT Torisel® and is NOT for human use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 111 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

become applicable in the aforementioned countries; and (viii) such O O similar laws and rules as may apply in various other countries. O O • Not available in some countries; not available to some institutions; H not available for some uses. O O O

HO O OH O OH HO O

O O O CH 3 Tifolar – see Pemetrexed, Disodium Salt, Heptahydrate H (Cat. No. P-7177 on page 84). O O OH N T-5096 Tinyatoxin, >99% H O O O CH O [TNX] [TYX] O 3 HO O OCH Size US$ ¤ £ ¥ 3 1 mg 122 90 76 10,000 5 mg 448 330 278 36,800 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 12-O-Tetradecanoylphorbol 13-Acetate M.W. 598.68 c H O [58821-95-7] — see Phorbol 12‑Myristate 13‑Acetate 36 38 8 (Cat. No. P‑1680 on page 87). WARNING: Irritant to skin and mucous membranes

4α-12-O-Tetradecanoylphorbol 13-Acetate — Storage: Store at or below -20 °C. Solubility: Soluble in see 4α‑Phorbol 12‑Myristate 13‑Acetate DMSO or ethanol. Disposal: A (Cat. No. P‑8880 on page 87). • Analog of resiniferatoxin (RTX, Cat. No. R-6712 on page 97); 40-epi-(N1-Tetrazolyl)-rapamycin — see Zotarolimus, Free Base 6-fold weaker than RTX in mouse ear erythema tests. (Cat. No. Z-9040 on page 128). 3 • Tinyatoxin inhibits specific [ H]RTX binding with a Ki of 0.8 nM, T-3250 Thapsigargin, >99% about three-fold weaker than for resiniferatoxin. Szallasi, A. and Blumberg, P.M. Brain Res. 547: 335-338 (1991). Size US$ ¤ £ ¥ • Please request Technical Note #28 for additional information. 1 mg 32 22 19 3,000 • Pharmaceutical formulations containing this compound, and anti- 5 mg 139 97 84 13,100 inflammatory, anti-viral and anti-psoriatic uses, are covered by 10 mg 245 171 148 23,100 U.S. patents 5,643,948 and 5,955,501. 25 mg 495 345 300 46,700 • Sold for laboratory or manufacturing purposes only; not for NOTE: Euro, Pound and Yen prices are revised regularly. human, medical, veterinary, food, or household use. Please visit www.LCLabs.com for our current prices.

M.W. 650.75 C34H50O12 [67526-95-8] M.I. 14: 9272 O H C WARNING: Irritant to skin and mucous membranes. 3 O O H H SPECIAL HAZARD: TUMOR PROMOTER. Wear gloves OH and mask when using this compound. Care must be taken O to prevent contact through all routes of exposure. HO O O Storage: Store at or below -20 °C. Solubility: Soluble in DMSO or ethanol. Disposal: A T-9104 Tipifarnib, Free Base, >99% • Potent, cell permeable IP3-independent intracellular calcium Synonyms: [R-115777] releaser. Takemura, H. et al. J. Biol. Chem. 264: 12266-12271 Related Terms: [Zarnestra] (1989). • Inhibits microsomal Ca2+-ATPase. Thastrup, O. et al. Size US$ ¤ £ ¥ Agents Actions 27: 17-23 (1989). 1 mg 78 60 52 8,700 • Rat mast cell histamine secretagogue. Rasmussen, U.S.B. et al. Prices 5 mg 179 138 118 20,000 Acta Pharm. Suecica 15: 133‑140 (1978). Patkar, S.A. et al. Reduced! 10 mg 337 261 223 37,700 Agents Actions 9: 53-57 (1979). 25 mg 578 447 382 64,600 • Mouse skin tumor promoter with potency somewhat weaker 50 mg 848 656 561 94,800 than teleocidin or PMA, but does not bind to protein kinase 100 mg 1290 997 853 144,200 C or induce ornithine decarboxylase activity. Hakii, H. et al. J. Cancer Res. Clin. Oncol. 111: 177‑181 (1986). 200 mg 1830 1415 1210 204,600 NOTE: Euro, Pound and Yen prices are revised regularly. • Stimulates arachidonic acid metabolism in macrophages. Please visit www.LCLabs.com for our current prices. Ohuchi, K. et al. J. Cancer Res. Clin. Oncol. 113: 319-324 (1987). M.W. 489.40 c H Cl N O [192185-72-1] • Please request Technical Note #15. 27 22 2 4 M.I. 14: 9458 • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 16 mg/mL with warming; soluble in ethanol at 12 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5‑10 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

112 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

CH • Tipifarnib, also known as R115777, is a potent, selective, 3 non-peptide inhibitor of farnesyl protein transferase that has N O significant antitumor effects in vivo. It competitively inhibited N the farnesylation of lamin B (IC = 0.86 nM) and K-RasB 50 N (IC = 7.9 nM) peptide substrates and inhibited the cell growth H N 50 H C 2 of ~75% of a panel of 53 human tumor cell lines tested. Tipifarnib 3 produced a prominent antiangiogenic response in LoVo human colon tumors, an antiproliferative response in CAPAN-2 human Cl

pancreatic tumors, and apoptosis in C32 human melanoma. Cl End, D.W. et al., “Characterization of the Antitumor Effects of the Selective Farnesyl Protein Transferase Inhibitor R115777 in Vivo T-6466 Tivozanib, Free Base, 99% and in Vitro.” Cancer Res. 61: 131‑137 (2001). Synonyms: [AV-951] [KRN-951] • Tipifarnib significantly reduced daunorubicin efflux in CCRF- CEM cells (IC50 < 0.5 µM). It also inhibited cellular proliferation Size US$ ¤ £ ¥ and induced apoptosis synergistically with daunorubicin. Tipifarnib has both P-glycoprotein inhibitory activity and farnesyl 5 mg 56 43 35 4,700 transferase inhibitory activity. Medeiros, B.C. et al., “The farnesyl 10 mg 79 60 49 6,600 transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 25 mg 122 93 75 10,200 gene product, P-glycoprotein, and demonstrates significant 50 mg 198 150 122 16,500 cytotoxic synergism against human leukemia cell lines.” 100 mg 322 245 199 26,900 Leukemia 21: 739‑746 (2007). 200 mg 399 303 247 33,300 • Tipifarnib significantly decreased (>85%) the proliferative index 250 mg 462 351 286 38,600 and increased apoptosis by about 5-fold in all mammary cancers 500 mg 1780 1353 1101 148,600 with HaRas mutations, whereas variable responses were observed 1 g 2990 2272 1849 249,700 in cancers without HaRas mutations. Lubet, R.A. et al., “Effects NOTE: Euro, Pound and Yen prices are revised regularly. of the farnesyl transferase inhibitor R115777 (Zarnestra) on Please visit www.LCLabs.com for our current prices. mammary carcinogenesis: prevention, therapy, and role of HaRas M.W. 454.86 c H ClN O [475108-18-0] mutations.” Mol. Cancer Ther. 5: 1073‑1078 (2006). 22 19 4 5 • Treatment with tipifarnib inhibited cell growth in vitro and Storage: Store at or below -20 ºC. Solubility: Soluble in tumor growth in vivo, caused increased apoptosis and decreased DMSO at 5 mg/mL with warming; very poorly soluble in proliferation, and reduced the cell turnover index. Wärnberg, F. ethanol; very poorly soluble in water; maximum solubility et al., “Effect of a farnesyl transferase inhibitor (R115777) on in plain water is estimated to be about 50-100 µM; buffers, ductal carcinoma in situ of the breast in a human xenograft model serum, or other additives may increase or decrease the and on breast and ovarian cancer cell growth in vitro and in vivo.” aqueous solubility. Disposal: A Breast Cancer Res. 8: R21‑R30 (2006). • Tivozanib, also known as AV-951, is a VEGF receptor tyrosine • Tipifarnib blocks the growth of human pancreatic adenocarcinoma kinase inhibitor. cell lines; this growth inhibition is related to regulation • Tivozanib strongly inhibited VEGFR-1, VEGFR-2, and in the extracellular signal-regulated kinases (ERK) and VEGFR-3 tyrosine kinases with IC50 values of 30, 6.5, and 15 phosphorylation levels of signal transducer and activators of nM, respectively. It also inhibited EphB2, PDGFR-α, PDGFR-β, transcription 3 (STAT3). Venkatasubbarao, K. et al., “Farnesyl c-Kit, and Tie2 tyrosine kinases with IC50 values of 24, 40, 49, Transferase Inhibitor (R115777)-Induced Inhibition of 78, and 78 nM, respectively. Furthermore, it inhibited several STAT3(Tyr705) Phosphorylation in Human Pancreatic Cancer other tyrosine kinases with IC50 values greater than for VEGFR-2. Cell Lines Require Extracellular Signal-Regulated Kinases.” Tivozanib markedly inhibited the ligand-induced phosphorylation Cancer Res. 65: 2861‑2871 (2005). of VEGFR-1, VEGFR-2, and VEGFR-3 in cellular assays, • Tipifarnib is the active ingredient in the drug sold under the trade with IC50 values of 0.21, 0.16, and 0.24 nM, respectively. name Zarnestra®. This drug is currently approved in at least one It strongly inhibited VEGF-dependent phosphorylation of country for use in elderly patients with newly diagnosed poor-risk MAPKs in HUVECs, with IC50 values of 0.13 and 0.18 nM acute myeloid leukemia. NOTE: THE TIPIFARNIB, FREE BASE for extracellular signal-regulated kinase 1 (ERK1) and ERK2, RESEARCH COMPOUND SOLD BY LC LABORATORIES IS respectively. It also inhibited the VEGF-induced proliferation ® NOT ZARNESTRA AND IS NOT FOR HUMAN USE. of HUVECs with an IC50 of 0.67 nM. Tivozanib inhibited tumor growth in vivo in athymic rat xenograft models of breast, • Our tipifarnib product is the free base, whose CAS number is colon, hepatic, lung, ovarian, pancreatic, and prostate tumors. given above. Chemical Abstracts Service also uses another CAS Nakamura, K. et al., “KRN951, a highly potent inhibitor of number for the same compound, namely 192185-68-5, but the vascular endothelial growth factor receptor tyrosine kinases, has entry in the CAS database for 192185-68-5 does not identify the antitumor activities and affects functional vascular properties.” stereochemistry. Cancer Res. 66: 9134‑9142 (2006). • Sold for laboratory or manufacturing purposes only; not for • A phase II clinical trial demonstrated an overall response rate of human, veterinary, food, or household use. 25% and a median progression-free survival time of 11.8 months • This product is offered for R&D use in accordance with (i) 35 in patients with advanced renal cell carcinoma treated with USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese tivozanib as a single agent. Hypertension and dysphonia were Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent the most frequent side effects. De Luca, A. and Normanno, N., Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. “Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) potential treatment of solid tumors.” IDrugs 13: 636‑645 (2010). and other common law exemptions of Canadian patent law; (vi) • Related CAS numbers: 682745-41-1 for the tivozanib Section 68B of the Patents Act of 1953 in New Zealand together monohydrochloride monohydrate. with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or • Sold for laboratory or manufacturing purposes only; not for become applicable in the aforementioned countries; and (viii) such human, veterinary, food, or household use. similar laws and rules as may apply in various other countries. • This product is offered for R&D use in accordance with (i) 35 • Not available in some countries; not available to some institutions; USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese not available for some uses. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6)

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 113 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

and other common law exemptions of Canadian patent law; (vi) • JAK3 plays an important role in pulmonary eosinophilia in the Section 68B of the Patents Act of 1953 in New Zealand together allergic mouse model. Tofacitinib, as a JAK3 inhibitor, represents with the amendment of same by the Statutes Amendment Bill of a potential therapy for treatment of allergic conditions associated 2002; (vii) such related legislation and/or case law as may be or with airway eosinophilia including asthma and rhinitis. Kudlacz, become applicable in the aforementioned countries; and (viii) such E. et al., “The JAK-3 inhibitor CP-690550 is a potent anti- similar laws and rules as may apply in various other countries. inflammatory agent in a murine model of pulmonary eosinophilia.” • Not available in some countries; not available to some institutions; Eur. J. Pharmacol. 582: 154-161 (2008). not available for some uses. • Tofacitinib was evaluated in murine collagen-induced (CIA) and

OCH rat adjuvant-induced (AA) models of rheumatoid arthritis (RA). 3 Tofacitinib dose-dependently reduced endpoints of disease in both OCH 3 RA models. The compound also inhibited inflammatory cell influx

O and joint damage. Milici, A.J. et al., “Cartilage preservation by O N O inhibition of Janus kinase 3 in two rodent models of rheumatoid H C 3 N arthritis.” Arthritis Res. Ther. 10: R14 (2008). N N

HH Cl • Tofacitinib effectively blocked allograft vasculopathy in the rat model of aorta transplantation by inhibiting JAK3. Rousvoal, G., TKI-258 — see Dovitinib, Free Base (Cat. No. D-3608 on page 31) and et al., “Janus kinase 3 inhibition with CP-690,550 prevents Dovitinib, Lactate Salt (Cat. No. D-3699 on page 32). allograft vasculopathy.” Transpl. Int. 19: 1014-1021 (2006). • Combination treatment of Tofacitinib with mycophenolate mofetil TNX — see Tinyatoxin (Cat. No. T-5096 on page 112). (MMF) significantly improved allograft survival in nonhuman T-1377 Tofacitinib, Free Base, >99% primates compared to treatment with MMF alone. Borie, D.C., Previous Names: CP690550, Tasocitinib et al., “Combined use of the JAK3 inhibitor CP-690,550 with mycophenolate mofetil to prevent kidney allograft rejection in Synonyms: [CP-690550] [Tasocitinib] nonhuman primates.” Transplantation 80: 1756-1764 (2005). Related Terms: [Xeljanz] • Tofacitinib (as the citrate salt) is the active ingredient in the drug product sold under the trade name Xeljanz®. This drug is Size US$ ¤ £ ¥ currently approved in at least one country for use in patients 10 mg 31 23 20 3,000 with moderately to severely active rheumatoid arthritis who have 25 mg 68 51 44 6,500 had an inadequate response or intolerance to methotrexate. THE 50 mg 97 73 63 9,300 TOFACITINIB, FREE BASE RESEARCH COMPOUND SOLD ® 100 mg 159 119 103 15,300 BY LC LABORATORIES IS NOT XELJANZ AND IS NOT 200 mg 234 175 151 22,500 FOR HUMAN USE. 500 mg 515 386 332 49,600 • Sold for laboratory or manufacturing purposes only; not for 1 g 774 580 499 74,500 human, medical, veterinary, food, or household use. 2 g 1370 1027 884 131,800 • This product is offered for R&D use in accordance with (i) 35 NOTE: Euro, Pound and Yen prices are revised regularly. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Please visit www.LCLabs.com for our current prices. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent M.W. 312.37 C H N O [477600-75-2] Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 16 20 6 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Storage: Store at or below -20 ºC. Solubility: Soluble in and other common law exemptions of Canadian patent law; (vi) DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; Section 68B of the Patents Act of 1953 in New Zealand together very poorly soluble in water; maximum solubility in plain with the amendment of same by the Statutes Amendment Bill of water is estimated to be about 10-20 µM; buffers, serum, 2002; (vii) such related legislation and/or case law as may be or or other additives may increase or decrease the aqueous become applicable in the aforementioned countries; and (viii) such solubility. Disposal: A similar laws and rules as may apply in various other countries. • This product was previously Cat. No. C-1377, CP690550 • Not available in some countries; not available to some institutions; and was also previously named Tasocitinib under the current not available for some uses. Cat. No. T-1377. • Please see also our other standard immunosuppressant products: • This is the free base form of tofacitinib. It is the citrate salt form - Ascomycin (Cat. No. A-1040 on page 7) (Cat. No. T-1399 on page 115), not the free base, that is used in the formulation of tofacitinib for in vivo use. - Cyclosporin A (Cat. No. C-6000 on page 25) • Tofacitinib is a novel Janus kinase 3 (JAK3) inhibitor. JAK3 is a - Everolimus (Cat. No. E-4040 on page 40) critical cytoplasmic tyrosine kinase in the signaling pathways of - Fingolimod, Hydrochloride Salt (Cat. No. F-4633 on page 42) multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are - FK-506 (Cat. No. F-4900 on page 42) associated with various T cell functions. - Pimecrolimus (Cat. No. P-6040 on page 91) • Preclinical and clinical data show that Tofacitinib, as an - Rapamycin (Cat. No. R-5000 on page 96) immunosuppressant, prevents organ transplant rejection and - Temsirolimus (Cat. No. T-8040 on page 111) alleviates the symptoms of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriasis. West, K., “CP-690550, - Zotarolimus, Free Base (Cat. No. Z-9040 on page 128)

a JAK3 inhibitor as an immunosuppressant for the treatment of H C rheumatoid arthritis, transplant rejection, psoriasis and other 3 H C N immune-mediated disorders.” Curr. Opin. Investig. Drugs 3 10: 491-504 (2009). N CN O • Tofacitinib showed greater antiproliferative and pro-apoptotic N activity against murine multipotent factor-dependent cell N N Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring H JAK2(V617F) compared with JAK2(WT). Manshouri, T., et al., “The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation.” Cancer Sci. 99: 1265-1273 (2008).

114 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

T-1399 Tofacitinib, Citrate Salt, >99% mTOR Inhibitor XII — see Torin 2, Free Base Synonyms: [CP-690550] [CP-690550 Citrate] (Cat. No. T‑8448 on page 116). [Tasocitinib] T-7887 Torin 1, Free Base, >99% Related Terms: [Xeljanz] Synonyms: [mTOR Inhibitor XI]

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 10 mg 31 23 20 3,000 10 mg 107 77 64 12,200 25 mg 68 51 44 6,500 New! 25 mg 242 174 145 27,500 50 mg 97 73 63 9,300 50 mg 387 278 232 44,000 100 mg 159 119 103 15,300 100 mg 642 462 386 72,900 200 mg 234 175 151 22,500 200 mg 984 707 591 111,800 500 mg 515 386 332 49,600 NOTE: Euro, Pound and Yen prices are revised regularly. 1 g 774 580 499 74,500 Please visit www.LCLabs.com for our current prices.

2 g 1370 1027 884 131,800 M.W. 607.62 C35H28F3N5O2 [1222998-36-8] NOTE: Euro, Pound and Yen prices are revised regularly. : Store at or below -20 ºC. : Soluble in Please visit www.LCLabs.com for our current prices. Storage Solubility DMSO. Disposal: A M.W. 504.49 c H N O•C H O [540737-29-9] 16 20 6 6 8 7 • Torin1 is a highly potent and selective ATP-competitive M.I. 14: 10489 mammalian target of rapamycin (mTOR) kinase inhibitor that Storage: Store at or below -20 ºC. Solubility: Soluble directly inhibited both complexes, mTORC1 and mTORC2, with in DMSO at 100 mg/mL; very poorly soluble in ethanol; IC50 values between 2 and 10 nM in in vitro kinase assays. It soluble in water at 6 mg/mL with warming; buffers, serum, prevented cell growth and proliferation to a far greater degree or other additives may increase or decrease the aqueous than rapamycin (see Rapamycin, Cat. No. R-5000 on page 96). solubility. Disposal: A However, these effects were independent of mTORC2 inhibition • This is the citrate salt form of tofacitinib. See Tofacitinib, Free and were instead dependent on inhibition of rapamycin-resistant Base (Cat. No. T-1377 on page 114) for further technical information. functions of mTORC1 that were necessary for cap-dependent It is this citrate salt form, not the free base, that is used in the translation and suppression of autophagy. These effects were formulation of tofacitinib for in vivo use. at least partly mediated through mTORC1-dependent and rapamycin-resistant phosphorylation of 4E-BP1. Thoreen, C.C. • Tofacitinib citrate is the active ingredient in the drug product sold ® et al., "An ATP-competitive mammalian target of rapamycin under the trade name Xeljanz . This drug is currently approved inhibitor reveals rapamycin-resistant functions of mTORC1." in at least one country for use in patients with moderately to J. Biol. Chem. 284: 8023‑8032 (2009). severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. THE TOFACITINIB, • Torin 1 and Torin 2 are potent antimalarials. Hanson, K.K. CITRATE SALT RESEARCH COMPOUND SOLD BY et al., "Torins are potent antimalarials that block replenishment LC LABORATORIES IS NOT XELJANZ® AND IS NOT FOR of Plasmodium liver stage parasitophorous vacuole membrane HUMAN USE. proteins." Proc. Natl. Acad. Sci. USA 110: E2838‑E2847 (2013). • Sold for laboratory or manufacturing purposes only; not for • Genetic and biochemical evidence obtained using rapamycin or human, medical, veterinary, food, or household use. torin 1 and Rheb (Ras homolog enriched in brain) demonstrated that pUL38 prevented endoplasmic reticulum stress-induced • This product is offered for R&D use in accordance with (i) 35 cell death independently of its role in mTORC1 activation. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Qian, Z. et al., "The human cytomegalovirus protein pUL38 Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent suppresses endoplasmic reticulum stress-mediated cell death Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. independently of its ability to induce mTORC1 activation." Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) J. Virol. 85: 9103‑9113 (2011). and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together • Sold for laboratory or manufacturing purposes only; not for with the amendment of same by the Statutes Amendment Bill of human, veterinary, food, or household use. 2002; (vii) such related legislation and/or case law as may be or • This product is offered for R&D use in accordance with (i) 35 become applicable in the aforementioned countries; and (viii) such USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese similar laws and rules as may apply in various other countries. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Not available in some countries; not available to some institutions; Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. not available for some uses. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) H C 3 Section 68B of the Patents Act of 1953 in New Zealand together O OH with the amendment of same by the Statutes Amendment Bill of H C N O 3 N CN 2002; (vii) such related legislation and/or case law as may be or O OH become applicable in the aforementioned countries; and (viii) such N HO OH similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; N N H O not available for some uses. Tomtovok — see its active ingredient, namely Afatinib, Free Base O H C F F (Cat. No. A-8644 on page 4). 3 N F Toposar — see its active ingredient, namely Etoposide N (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, O Free Acid (Cat. No. E-4444 on page 39). N N Topotecin — see Irinotecan, Hydrochloride Salt, Trihydrate (Cat. No. I-4122 on page 57). mTOR Inhibitor XI — see Torin 1, Free Base N (Cat. No. T‑7887 on page 115).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 115 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

T-8448 Torin 2, Free Base, >99% Torkinib — see PP242, Free Base (Cat. No. P-6666 on page 93). Synonyms: [mTOR Inhibitor XII] Tovok — see its active ingredient, namely Afatinib, Free Base (Cat. No. A-8644 on page 4). Size US$ ¤ £ ¥ 5 mg 73 52 44 8,300 T-2304 Tozasertib, Free Base, >99% New! 10 mg 108 78 65 12,300 [MK-0457] [VX-680] [VX6] 25 mg 228 164 137 25,900 50 mg 370 266 222 42,000 Size US$ ¤ £ ¥ 100 mg 639 459 384 72,600 25 mg 28 21 18 2,800 250 mg 978 703 587 111,100 50 mg 49 38 32 4,900 NOTE: Euro, Pound and Yen prices are revised regularly. 100 mg 89 68 58 8,900 Please visit www.LCLabs.com for our current prices. 250 mg 205 157 135 20,400 300 mg 237 182 156 23,600 M.W. 432.40 c24H15F3N4O [1223001-51-1] Storage: Store at or below -20 ºC. Solubility: Soluble in 500 mg 372 285 244 37,000 DMSO. Disposal: A 1 g 614 470 403 61,100 2 g 1110 850 729 110,400 • Torin 2 is a highly potent and selective ATP-competitive NOTE: Euro, Pound and Yen prices are revised regularly. mammalian target of rapamycin (mTOR) kinase inhibitor. Torin 2 Please visit www.LCLabs.com for our current prices. inhibited cellular mTOR activity with an IC of 0.25 nM and 50 M.W. 464.59 c H N OS [639089-54-6] exhibited 800-fold selectivity over PI3K (IC50 = 200 nM) and 23 28 8 over 100-fold binding selectivity over 440 other protein kinases. Storage: Store at or below -20 °C. Solubility: Soluble Liu, Q. et al., "Discovery of 9-(6-aminopyridin-3-yl)-1-(3- in DMSO at 100 mg/mL; very poorly soluble in ethanol; (trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one very poorly soluble in water; maximum solubility in plain (Torin2) as a potent, selective, and orally available mammalian water is estimated to be about 10-30 µM; buffers, serum, target of rapamycin (mTOR) inhibitor for treatment of cancer." or other additives may increase or decrease the aqueous J. Med. Chem. 54: 1473‑1480 (2011). solubility. Disposal: A • In addition to mTOR, torin 2 also exhibited potent biochemical • Tozasertib is a potent inhibitor of all aurora kinases, including and cellular activity against phosphatidylinositol-3 kinase-like the A, B and C isotypes (Ki = 0.6 nM, 18 nM and 4.6 nM, (PI3K-like) kinase family kinases including ATM (IC = 28 nM), 50 respectively). It also inhibits ABL kinase (Ki = 30 nM), an ATR (IC = 35 nM), and DNA-PK (IC = 118 nM), the inhibition 50 50 imatinib resistant ABL mutant (T315I) kinase (Ki = 42 nM), of which sensitized cells to irradiation. Treatment with torin and Flt-3 ( Ki = 30 nM). Tozasertib binds to an inactive 2 for 24 hours resulted in strong growth inhibition of cancer aurora conformation. Cheetham, G.M. et al., “Structural cells in vitro. Single-agent treatment with torin 2 in vivo did not basis for potent inhibition of the aurora kinases and a T315I show significant efficacy against KRAS-driven lung tumors, multi-drug resistant mutant form of Abl kinase by VX-680.” but the combination of torin 2 with mitogen-activated protein/ Cancer Lett. 251: 323‑329 (2007). extracellular signal-regulated kinase inhibitor AZD6244 (see • Tozasertib has a similar binding affinity to ABL1 kinase Selumetinib, Free Base, Cat. No. S-4490 on page 104) demonstrated (Kd = 20 nM) and mutated ABL1(T351I) kinase (Kd = 5 a significant growth inhibition. Liu, Q. et al., "Characterization of nM). It inhibits the growth of cells expressing wild type and Torin 2, an ATP-competitive inhibitor of mTOR, ATM, and ATR." mutated BCR-ABL, including T315I, with an IC50 of 200 nM. Cancer Res. 73: 2574‑2586 (2013). Carter, T.A. et al., “Inhibition of drug-resistant mutants of ABL, • Torin 1 and torin 2 are potent antimalarials. Hanson, K.K. et al., KIT, and EGF receptor kinases.” Proc. Natl. Acad. Sci. U.S.A. "Torins are potent antimalarials that block replenishment of 102: 11011‑11016 (2005). Plasmodium liver stage parasitophorous vacuole membrane • Tozasertib inhibits cell cycle progression, induces apoptosis and proteins." Proc. Natl. Acad. Sci. USA 110: E2838‑E2847 (2013). blocks tumor growth in varieties of in vivo xenograft models, • Sold for laboratory or manufacturing purposes only; not for including leukemia, colon and pancreatic tumors. Harrington, E.A. human, veterinary, food, or household use. et al., “VX-680, a potent and selective small-molecule inhibitor of • This product is offered for R&D use in accordance with (i) 35 the aurora kinases, suppresses tumor growth in vivo.” Nat. Med. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 10: 262-267 (2004). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Tozasertib has shown antitumor effects in patients with T315I Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. ABL-mutated chronic myeloid leukemia (CML) or Philadelphia Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) chromosome (Ph)–positive acute lymphocytic leukemia and other common law exemptions of Canadian patent law; (vi) (ALL). Giles, F.J. et al., “MK-0457, a novel kinase inhibitor, Section 68B of the Patents Act of 1953 in New Zealand together is active in patients with chronic myeloid leukemia or acute with the amendment of same by the Statutes Amendment Bill of lymphocytic leukemia with the T315I BCR-ABL mutation.” 2002; (vii) such related legislation and/or case law as may be or Blood 109: 500‑502 (2007). become applicable in the aforementioned countries; and (viii) such • Sold for laboratory or manufacturing purposes only; not for similar laws and rules as may apply in various other countries. human, medical, veterinary, food, or household use. • Not available in some countries; not available to some institutions; • This product is offered for R&D use in accordance with (i) 35 not available for some uses. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese F F Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent F Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K.

O Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) H N N 2 N Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such N similar laws and rules as may apply in various other countries. Torisel — see its active ingredient, namely Temsirolimus • Not available in some countries; not available to some institutions; (Cat. No. T-8040 on page 111). not available for some uses.

116 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• For solid tumors, RAF/RAS mutation and the expression of the N DUSP6 gene were strong predictors of sensitivity to trametinib. S N N O Among hematologic cell lines, acute and chronic myeloid

N leukemia cell lines were particularly sensitive to trametinib. Jing, J. N et al., “Comprehensive predictive biomarker analysis for MEK H N inhibitor GSK1120212.” Mol. Cancer Ther. 11: 720‑729 (2012). H • Trametinib had favorable antitumor activities against colorectal N N cancers in vitro and in vivo. It exhibited an additive or a H synergistic effect in combination with other chemotherapy agents TPA — see Phorbol 12-Myristate 13-Acetate including 5-fluorouracil, oxaliplatin, or SN-38. Yamaguchi, T. (Cat. No. P-1680 on page 87). et al., “Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and 4α-TPA — see 4α-Phorbol 12-Myristate 13-Acetate in vivo.” Int. J. Oncol. 39: 23‑31 (2011). (Cat. No. P-8880T-2304-2006-11-21-kedRev.SKC on page 87). • Trametinib is the active ingredient in the drug product sold T-8123 Trametinib, >99% under the trade name Mekinist®. This drug is currently approved in at least one country for use in patients with unresectable or Synonyms: [GSK-1120212] [JTP-74057] metastatic melanoma with BRAF V600E or V600K mutations. Related Terms: [Mekinist] Note: The Trametinib research compound sold by LC Laboratories is not Mekinist® and is not Size US$ ¤ £ ¥ for human use. 10 mg 39 29 25 3,800 • Related CAS number: 1187431-43-1 for the dimethylsulfoxide Prices 25 mg 69 52 44 6,600 solvate of trametinib. Reduced! 50 mg 88 66 57 8,500 • Another CAS number previously assigned to Trametinib, namely 100 mg 121 91 78 11,600 1204531-14-5, has been deleted by CAS and is no longer in use. 200 mg 184 138 119 17,700 • Sold for laboratory or manufacturing purposes only; not for 500 mg 398 298 257 38,300 human, veterinary, food, or household use. 1 g 697 523 449 67,100 • This product is offered for R&D use in accordance with (i) 35 2 g 1290 967 832 124,100 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese NOTE: Euro, Pound and Yen prices are revised regularly. Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Please visit www.LCLabs.com for our current prices. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. M.W. 615.39 c H FIN O [871700-17-3] Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) 26 23 5 4 and other common law exemptions of Canadian patent law; (vi) Storage: Store at or below -20 ºC. Solubility: Soluble in Section 68B of the Patents Act of 1953 in New Zealand together DMSO at 20 mg/mL with warming; very poorly soluble in with the amendment of same by the Statutes Amendment Bill of ethanol; very poorly soluble in water; maximum solubility 2002; (vii) such related legislation and/or case law as may be or in plain water is estimated to be about 5-10 µM; buffers, become applicable in the aforementioned countries; and (viii) such serum, or other additives may increase or decrease the aqueous solubility. Disposal: A similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; • Trametinib is a selective MEK inhibitor. not available for some uses. • Trametinib inhibited MEK1/2 kinase activity, prevented Raf- H dependent MEK phosphorylation, and produced prolonged N CH p-ERK1/2 inhibition. It blocked the cell growth potently in 3

most tumor lines with mutant BRAF or Ras. In xenograft O CH tumor models, trametinib inhibited tumor growth, possibly by 3 sustained suppression of p-ERK1/2, inhibition of tumor Ki67, O N O and stimulation of p27Kip1/CDKN1B. The largest antitumor N N effect in vivo was among tumors harboring mutant BRAF or Ras. H C Gilmartin, A.G. et al., “GSK1120212 (JTP-74057) is an inhibitor 3 N O of MEK activity and activation with favorable pharmacokinetic H properties for sustained in vivo pathway inhibition.” Clin. Cancer Res. 17: 989‑1000 (2011). I F • A phase 1 clinical trial demonstrated substantial clinical Transplatin — see Oxaliplatin (Cat. No. O-7111 on page 79). activity of trametinib in human melanoma. Falchook, G.S. et al., “Activity of the oral MEK inhibitor trametinib in patients 4',5,7-Trihydroxyisoflavone — see Genistein with advanced melanoma: a phase 1 dose-escalation trial.” (Cat. No. G-6055 on page 48). Lancet Oncol. 13: 782‑789 (2012). TXD-258 — see Cabazitaxel (Cat. No. C-2581 on page 15). • Trametinib improved rates of progression-free and overall survival among patients who had metastatic melanoma with Tykerb — see its active ingredient, namely Lapatinib Di-p- a BRAF V600E or V600K mutation when compared with Toluenesulfonate Salt (Cat. No. L-4804 on page 63) and dacarbazine or paclitaxel. Flaherty, K.T. et al., “Improved Lapatinib, Free Base (Cat. No. L-4899 on page 62). survival with MEK inhibition in BRAF-mutated melanoma.” N. Engl. J. Med. 367: 107‑114 (2012). • Both trametinib and leflunomide can suppress adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) development completely. In the CIA model, trametinib, but not leflunomide, inhibited collagen-reactive T-cell proliferation ex vivo, whereas leflunomide, but not trametinib, inhibited anti- collagen antibody production. Yamaguchi, T. et al., “Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide.” Inflamm. Res. 61: 445‑454 (2012).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 117 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• Sold for laboratory or manufacturing purposes only; not for T-9142 Tyrphostin AG 490, >99% human, medical, veterinary, food, or household use. [AG 490] [Tyrphostin B42] O HO Size US$ ¤ £ ¥ N H 10 mg 42 31 27 4,100 CN 25 mg 69 52 44 6,800 HO 50 mg 88 66 57 8,700 100 mg 115 86 74 11,400 T-7310 Tyrphostin AG 1478, Free Base, >99% 250 mg 232 173 149 22,900 [AG 1478] [4-(3'-Chloroanilino)-6,7- 300 mg 258 193 166 25,500 dimethoxyquinazoline] 1 g 598 447 384 59,000 Size US$ ¤ £ ¥ NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 25 mg 71 49 43 6,700 100 mg 219 153 133 20,700 M.W. 294.30 c17H14N2O3 [134036-52-5] 500 mg 725 505 439 68,400 Storage: Store at or below -20 °C. Solubility: Soluble in DMSO at 200 mg/mL; soluble in ethanol at 16 mg/mL; 1 g 1160 809 703 109,500 very poorly soluble in water; maximum solubility in plain NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. water is estimated to be about 50-100 µM; buffers, serum, or other additives may increase or decrease the aqueous M.W. 315.75 C16H14ClN3O2 [175178-82-2] solubility. Appearance: Cream solid. Disposal: A Storage: Store at or below -20 °C. Solubility: Soluble in • Specific and potent JAK-2 protein tyrosine kinase inhibitor. Also DMSO at 50 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility inhibits EGF receptor autophosphorylation, with an IC50 of 100 nM. Inhibits DNA synthesis and cell growth; induces apoptosis. in plain water is estimated to be about 10-20 µM; buffers, Levitzki, A., “Tyrphostins—potential antiproliferative agents serum, or other additives may increase or decrease the and novel molecular tools.” Biochem. Pharmacol. 40: 913- aqueous solubility. Appearance: White solid. Disposal: A 918 (1990). Gazit, A. et al., “Tyrphostins. 2. Heterocyclic and • Very potent EGF receptor kinase (tyrosine kinase) inhibitor alpha-substituted benzylidenemalononitrile tyrphostins as potent (IC = 3 nM). Very weak on PDGF receptor and HER2-NEU inhibitors of EGF receptor and ErbB2/neu tyrosine kinases.” 50 kinases (IC50 >100 µM). Osherov, N. and Levitski, A., “Epidermal- J. Med. Chem. 34: 1896‑1907 (1991). growth-factor-dependent activation of the src-family kinases.” • Inhibits the growth of leukemic cells in vitro and in vivo. Blocks Eur. J. Biochem. 225: 1047‑1053 (1994). Levitski, A. and Gazit, STAT3 constitutive activation and inhibits both interleukin A., “Tyrosine kinase inhibition: an approach to drug development.” 2(IL2)-induced and spontaneous growth of Mycosis fungoides Science 267: 1782‑1788 (1995). (MF), a cutaneous T cell lymphoma. Growth of human ovarian • Reversibly inhibits (IC50 = 9.8 µM) the rat brain Kv1.5 and breast cancer cell lines was shown to be significantly potassium channel in vitro in a non-protein-tyrosine-kinase- suppressed by AG 490 via JAK/STAT3 pathway inhibition. mediated manner. Choi, B.H. et al., “Direct inhibition of the Meydan, N. et al., “Inhibition of acute lymphoblastic leukaemia cloned Kv1.5 channel by AG-1478, a tyrosine kinase inhibitor.” by a Jak-2 inhibitor.” Nature 379: 645‑648 (1996). Nielsen M. Am. J. Physiol. Cell Physiol. 282: C1461‑C1468 (2002). et al., “Constitutive activation of a slowly migrating isoform • This product is the free base, which is best dissolved in DMSO. of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines.” • Sold for laboratory or manufacturing purposes only; not for Proc Natl Acad Sci USA. 94: 6764‑6769 (1997). Eriksen, K.W. human, medical, veterinary, food, or household use. et al., “Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells.” HN Cl Leukemia 15: 787‑793 (2001). Burke, W.M. et al., “Inhibition of MeO constitutively active Stat3 suppresses growth of human ovarian N and breast cancer cells.” Oncogene 20: 7925‑7934 (2001). Levitzki, A., “Tyrosine kinases as targets for cancer therapy.” MeO N Eur J Cancer 38 Suppl 5: S11‑S18 (2002). Burdelya L. et al., “Combination therapy with AG-490 and interleukin 12 Tyrphostin B42 — see Tyrphostin AG 490 achieves greater antitumor effects than either agent alone.” (Cat. No. T-9142 on page 118). Mol Cancer Ther 11: 893‑899 (2002). Tyverb — see its active ingredient, namely Lapatinib Di-p- • AG 490 is a JAK3/STAT, JAK3/AP-1, and JAK3/ Toluenesulfonate Salt (Cat. No. L-4804 on page 63) and MAPK signaling pathway inhibitor and also blocks JAK3 Lapatinib, Free Base (Cat. No. L-4899 on page 62). autophosphorylation. Kirken, R.A. et al., “Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction TYX — see Tinyatoxin (Cat. No. T-5096 on page 112). and cellular proliferation of antigen-activated human T cells.” U-29135 — see Geldanamycin (Cat. No. G-4500 on page 46). J. Leukoc. Biol. 65: 891‑899 (1999). Wang, L.H. et al., “JAK3, STAT, and MAPK signaling pathways as novel molecular U-101440E — see Irinotecan, Hydrochloride Salt, Trihydrate targets for the tyrphostin AG-490 regulation of IL-2-mediated (Cat. No. I-4122 on page 57). T cell response.” J. Immunol. 162: 3897‑3904 (1999). De Vos, J. et al., “JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells.” Br. J. Haematol. 109: 823‑828 (2000). • Previously sold as “Tyrphostin B42”; the catalog number has not changed. • Please request Technical Note #22 for additional information.

118 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

U-6770 U0126, >99% V-9402 Vandetanib, Free Base, >99% [Zactima] [ZD6474] Size US$ ¤ £ ¥ 25 mg 52 42 34 4,100 Size US$ ¤ £ ¥ 100 mg 68 52 43 5,600 25 mg 44 34 29 4,900 250 mg 162 124 102 13,200 50 mg 56 43 37 6,300 300 mg 189 144 119 15,400 100 mg 87 67 58 9,700 1 g 335 256 211 27,400 200 mg 142 110 94 15,900 NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. 250 mg 172 133 114 19,200 500 mg 262 203 173 29,300 M.W. 380.49 c18H16N6S2 [109511-58-2] 1 g 475 367 314 53,100 Storage: Store at or below -20 °C. Solubility: Soluble 2 g 854 660 565 95,500 in DMSO at 200 mg/mL; very poorly soluble in ethanol; NOTE: Euro, Pound and Yen prices are revised regularly. very poorly soluble in water; maximum solubility in plain Please visit www.LCLabs.com for our current prices. water is estimated to be about 10‑50 µM; buffers, serum, M.W. 475.35 C H BrFN O [443913-73-3] or other additives may increase or decrease the aqueous 22 24 4 2 solubility. Appearance: White solid. Disposal: A M.I. 14: 10249 • Selective inhibitor of the mitogen-activated protein kinase Storage: Store at or below -20 °C. Solubility: Soluble in kinases, MEK-1 and MEK-2, with 100-fold higher potency DMSO at 30 mg/mL; soluble in ethanol at 10 mg/mL with than PD 98059, but is, at most, a weak inhibitor of PKC, Raf, warming; very poorly soluble in water; maximum solubility ERK, JNK, MEKK, MKK-3, MKK-4/SEK, MKK-6, Abl, Cdk2 in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the and Cdk4. U0126 is an inhibitor of AP-1 transactivation in aqueous solubility. Appearance: White solid. Disposal: A cell-based reporter assays. Favata, M.F. et al., “Identfication of a novel inhibitor of mitogen-activated protein kinase kinase.” • Vandetanib inhibits VEGFR-dependent tumor angiogenesis J. Biol. Chem. 273: 18623‑18632 (1998); DeSilva, D.R. et al., and EGFR- and RET-dependent tumor cell proliferation and “Inhibition of mitogen-activated protein kinase kinase blocks survival. Herbst, R.S. et al., “Vandetanib (ZD6474): an orally T cell proliferation but does not induce or prevent anergy.” available receptor tyrosine kinase inhibitor that selectively J. Immuol. 160: 4175‑4181 (1998); Scherle, P.A. et al., “Inhibition targets pathways critical for tumor growth and angiogenesis.” of MAP kinase kinase prevents cytokine and prostaglandin Expert Opin. Investig. Drugs 16: 239‑249 (2007). E2 production in lipopolysaccharide-stimulated monocytes.” • The IC50 values for vandetanib in HT-29 and LoVo cells are J. Immuol. 161: 5681‑5686 (1998). 10-80 µM and 3.5-16 µM, respectively, when the exposure • Our U0126 is highly purified. In crystalline form and in aprotic times are from 18 hours to 3 days. Azzariti, A. et al., “Prolonged solvents it is a single chemical entity. However, it appears that, in exposure of colon cancer cells to the epidermal growth factor solution in protic solvents, U0126 exists as a mixture of isomers. receptor inhibitor gefitinib (Iressa™) and to the antiangiogenic This phenomenon does not affect overall biological activity. Note agent ZD6474: Cytotoxic and biomolecular effects.” that DMSO normally contains water so that it behaves, in this World J. Gastroenterol. 12: 5140‑5147 (2006). case, as a protic solvent. (PKC Pharmaceuticals, Inc., unpublished • Vandetanib is a potent, p.o. active, low molecular weight inhibitor results.) of kinase insert domain-containing receptor [KDR/vascular • We note that U0126 is offered for sale by Sigma under the name endothelial growth factor receptor (VEGFR) 2] tyrosine kinase

“U0126 Ethanolate”. This “ethanolate” nomenclature is somewhat activity (IC50 = 40 nM). This compound has some additional ambiguous because “ethanolate” is often taken to mean “ethoxide activity against the tyrosine kinase activity of fms-like tyrosine

anion” (not correct for this product) rather than “neutral ethanol kinase 4 (VEGFR3; IC50 = 110 nM) and epidermal growth

included as solvent of crystallization with the primary compound” factor receptor (EGFR/HER1; IC50 = 500 nM) but demonstrates as presumably intended by Sigma. The level of solvent in our selectivity relating to a range of other tyrosine and serine- U0126 product is found on the Certificate of Analysis for each threonine kinases. The activity of vandetanib against KDR tyrosine lot. Small amounts of water or other solvent of crystallization kinase may explain its potent inhibition of vascular endothelial affect the molecular weight but not the biological properties of the growth factor A-stimulated human umbilical vein endothelial

U0126 itself. cell proliferation in vitro (IC50 = 60 nM). Wedge, S.R. et al., • Sold for laboratory or manufacturing purposes only; not for “ZD6474 Inhibits Vascular Endothelial Growth Factor Signaling, human, medical, veterinary, food, or household use. Angiogenesis, and Tumor Growth following Oral Administration.” Cancer Res. 62: 4645‑4655 (2002).

NH2 CN • A dose-dependent inhibition of EGFR tyrosine kinase activity S was observed after treatment with vandetanib (IC of ~0.25 NH 50 2 µM). Vandetanib also inhibited colony formation of seven H N 2 cancer cell lines in soft agar with IC ’s ranging between 0.5 NC S 50 and 1 µM. Ciardiello, F. et al., “Antitumor Effects of ZD6474, a Small Molecule Vascular Endothelial Growth Factor H N 2 Receptor Tyrosine Kinase Inhibitor, with Additional Activity against Epidermal Growth Factor Receptor Tyrosine Kinase.” Clin. Cancer Res. 9: 1546‑1556 (2003). • Vandetanib is the active ingredient in the drug sold under the trade name Zactima®. The drug is approved in at least one country for treatment of patients with follicular, medullary, anaplastic, and locally advanced and metastatic papillary thyroid cancer. NOTE: the vandetanib sold by LC Laboratories is NOT Zactima® and is NOT for human use. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 119 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent migration dose dependently (IC50 = 58 nM). Vatalanib inhibited

Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. tumor cell proliferation (IC50’s of 17 µM and 18 µM for A431 and Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) DU145 cells, respectively) and sprout formation in rat aortas (IC50 and other common law exemptions of Canadian patent law; (vi) = 675 nM). Wood, J.M. et al., “PTK787/ZK 222584, a Novel and Section 68B of the Patents Act of 1953 in New Zealand together Potent Inhibitor of Vascular Endothelial Growth Factor Receptor with the amendment of same by the Statutes Amendment Bill of Tyrosine Kinases, Impairs Vascular Endothelial Growth Factor- 2002; (vii) such related legislation and/or case law as may be or induced Responses and Tumor Growth after Oral Administration.” become applicable in the aforementioned countries; and (viii) such Cancer Res. 60: 2178‑2189 (2000). similar laws and rules as may apply in various other countries. • Sold for laboratory or manufacturing purposes only; not for • Not available in some countries; not available to some institutions; human, medical, veterinary, food, or household use. not available for some uses. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese N Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent O N Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) N O and other common law exemptions of Canadian patent law; (vi) NH Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of

F Br 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such Vargatef — see its active ingredient, namely Nintedanib, Free Base similar laws and rules as may apply in various other countries. (Cat. No. N-9077 on page 72) and Nintedanib, Ethanesulfonate • Not available in some countries; not available to some institutions; Salt (Cat. No. N-9055 on page 73). not available for some uses. V-8303 Vatalanib, Dihydrochloride Salt, >99% Cl . 2HCl [CGP 79787] [PTK 787] [ZK 222584] NH Size US$ ¤ £ ¥ N 25 mg 39 32 25 3,100 N 100 mg 68 52 43 5,600 200 mg 95 73 60 7,800 250 mg 106 81 67 8,700 N 500 mg 198 151 125 16,200 1 g 364 278 229 29,700 VCR sulfate – see Vincristine, Sulfate Salt 2 g 596 455 375 48,700 (Cat. No. V-8400 on page 122). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Velban — see its active ingredient, namely Vinblastine, Sulfate Salt (Cat. No. V-7300 on page 121). M.W. 419.73 C20H15ClN4 •2HCl [212141-51-0] M.I. 14: 9939 Velbe — see its active ingredient, namely Vinblastine, Sulfate Salt Storage: Store at or below -20 °C. Solubility: Soluble in (Cat. No. V-7300 on page 121). DMSO at 10-20 mg/mL with warming; very poorly soluble Velcade — see its active ingredient, namely in ethanol; soluble in water at 100 mg/mL; buffers, serum, Bortezomib, Free Base (Cat. No. B-1408 on page 11). or other additives may increase or decrease the aqueous solubility. Disposal: A Velsar — see its active ingredient, namely Vinblastine, Sulfate Salt (Cat. No. V-7300 on page 121). • Vatalanib is a potent, orally active, selective inhibitor of the VEGFR tyrosine kinases VEGFR-1 (Flt-1) and VEGFR-2 V-2800 Vemurafenib, Free Base, >99% (FLK-1/KDR), with slightly higher potency against the latter. At higher concentrations, other tyrosine kinases are also Synonyms: [PLX4032] [R7204] [RG7204] inhibited, including PDGFR-β, c-KIT, and c-FMS. In contrast, [RO5185426] vatalanib is not active against the EGFR, fibroblast growth Related Terms: [Zelboraf] factor receptor-1, c-MET, and TIE-2 or intracellular kinases such as c-SRC, c-ABL, and protein kinase C-α. Lin, B. et al., Size US$ ¤ £ ¥ “The vascular endothelial growth factor receptor tyrosine kinase 5 mg 25 18 15 3,000 inhibitor PTK787/ZK222584 inhibits growth and migration of Prices 10 mg 39 29 23 4,700 multiple myeloma cells in the bone marrow microenvironment.” Reduced! 25 mg 69 51 41 8,300 Cancer Res. 62: 5019‑5026 (2002). Rini, B.I. and Small, E.J., 50 mg 98 72 58 11,800 “Biology and clinical development of vascular endothelial 100 mg 169 125 100 20,300 growth factor-targeted therapy in renal cell carcinoma.” 200 mg 297 219 175 35,700 J. Clin. Oncol. 23: 1028‑1043 (2005). 500 mg 465 343 274 55,900 • Vatalanib is taken up by cells to reach its intracellular 1 g 777 574 458 93,400 target, as shown by its effects on receptor phosphorylation tested in cell-based assays. Measurement of VEGF- 2 g 1290 953 760 155,100 NOTE: Euro, Pound and Yen prices are revised regularly. induced autophosphorylation of KDR in a double antibody Please visit www.LCLabs.com for our current prices. chemiluminescence assay, using either HUVECs or CHO cells

transfected with the KDR receptor, showed that vatalanib inhibits M.W. 489.92 c23H18ClF2N3O3S [918504-65-1]

VEGF-induced phosphorylation with an IC50 of 17 nM and 34 Storage: Store at or below -20 ºC. Solubility: Soluble nM for HUVECs and CHO cells, respectively. Vatalanib inhibited in DMSO at 100 mg/mL; very poorly soluble in ethanol; thymidine incorporation induced by VEGF in HUVECs with an very poorly soluble in water; maximum solubility in plain

IC50 of 7.1 nM. In concentrations up to 1 µM, neither vatalanib water is estimated to be about 25-50 µM; buffers, serum, nor SU5416 inhibited the response to bFGF or serum. In a cell or other additives may increase or decrease the aqueous migration assay, vatalanib inhibited VEGF-induced HUVEC solubility. Disposal: A

120 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

• NOTE: As of September, 2011 the current correct CAS number for Vepesid — see its active ingredient, namely Etoposide vemurafenib, also known as PLX4032, is given above. Chemical (Cat. No. E-4488 on page 38) and Etoposide 4'-Phosphate, Abstracts Service recently canceled another CAS number, Free Acid (Cat. No. E-4444 on page 39). 1029872-54-5, that had previously been used for vemurafenib under its older name, PLX4032. However, this canceled number VER-52296 — see NVP-AUY922, Free Base remains in wide use and receives the vast majority of hits on (Cat. No. N-5300 on page 74). Google. Vinblastine hydrogen sulfate — see Vinblastine, Sulfate Salt • Vemurafenib inhibited ERK1/2 in the highly sensitive (Cat. No. V-7300 on page 121). BRAF(V600E/K) cells, while it activated the pathway in the (resistant) BRAF(WT) cells. Halaban, R. V-7300 Vinblastine, Sulfate Salt, >98% et al., “PLX4032, a selective BRAF(V600E) kinase Synonyms: [29060-LE] [Nincaluicolflastine] inhibitor, activates the ERK pathway and enhances cell [Vinblastine hydrogen sulfate] migration and proliferation of BRAF melanoma cells.” [Vincaleucoblastine sulfate] [VLB sulfate] Pigment Cell Melanoma Res. 23: 190‑200 (2010). Related Terms: [Alkaban-AQ] [Exal] [Rozevin sulfate] • Using an IC50g cutoff of 1 µM, 13 of 35 cell lines tested showed sensitivity to vemurafenib, 16 were resistant, and 6 were [Velban] [Velbe] [Velsar] intermediate in sensitivity. Vemurafenib caused growth inhibition, Size US$ ¤ £ ¥ G0/G1 arrest, and apoptosis in the sensitive cell lines. A BRAF mutation favored but did not guarantee a sensitive response, while 10 mg 39 29 25 3,500 cells bearing a neuroblastoma RAS viral oncogene homolog 25 mg 51 38 32 4,600 mutation or wild-type BRAF were resistant. Tap, W.D. et al., 50 mg 69 51 44 6,300 “Pharmacodynamic characterization of the efficacy signals 100 mg 95 71 60 8,600 due to selective BRAF inhibition with PLX4032 in malignant 200 mg 128 95 81 11,600 melanoma.” Neoplasia 12: 637‑649 (2010). 500 mg 229 170 145 20,800 • Vemurafenib inhibited the growth of B-Raf V600E‑positive 1 g 423 314 268 38,400 melanomas in vitro and in vivo. Lee, J.T. et al., “PLX4032, 2 g 756 562 478 68,700 a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas.” 5 g 1620 1203 1025 147,200 NOTE: Euro, Pound and Yen prices are revised regularly. Pigment Cell Melanoma Res. 23: 820‑827 (2010). Please visit www.LCLabs.com for our current prices. • Vemurafenib selectively inhibited the RAF/MEK/ERK pathway M.W. 909.05 c H N O •H SO [143-67-9] in BRAF mutant cells and induced regression of BRAF mutant 46 58 4 9 2 4 xenografts. However, no tumor regression occurred in patients M.I. 14: 9982 until greater than 80% inhibition of ERK phosphorylation in Storage: Store at or below -20 ºC. Solubility: Poorly the tumors was reached. Bollag, G. et al., “Clinical efficacy of soluble in ethanol; soluble in water at 50 mg/mL; buffers, a RAF inhibitor needs broad target blockade in BRAF-mutant serum, or other additives may increase or decrease the melanoma.” Nature 467: 596‑599 (2010). aqueous solubility. Disposal: A • Treatment of patients with metastatic melanoma that carry the • Vinblastine is an antimicrotubule drug that has been used to V600E BRAF mutation with vemurafenib resulted in complete or treat various cancers. Interruption of microtubule structure by partial tumor regression in the majority of patients. Flaherty, K.T. antimicrotubule drugs results in induction of tumor suppressor et al., “Inhibition of mutated, activated BRAF in metastatic gene p53 and inhibitor of cyclin-dependent kinases p21WAF1/ melanoma.” N. Engl. J. Med. 363: 809‑819 (2010). CIP1, and phosphorylation of Bcl-2, which lead to apoptosis in • Vemurafenib is the active ingredient in the drug product sold under cancer cells. Wang, L.G. et al., “The effect of antimicrotubule the trade name Zelboraf®. This drug is currently approved in at agents on signal transduction pathways of apoptosis: a review.” least one country for use in patients with late-stage melanoma. Cancer Chemother. Pharmacol. 44: 355‑361 (1999). NOTE: THE VEMURAFENIB, FREE BASE RESEARCH • Combination chemotherapy with Adriamycin – see Doxorubicin, COMPOUND SOLD BY LC LABORATORIES IS NOT Hydrochloride Salt (Cat. No. D-4000 on page 33 and Doxorubicin, ZELBORAF® AND IS NOT FOR HUMAN USE. Free Base (Cat. No. D-4099 on page 32) – bleomycin, vinblastine, • Sold for laboratory or manufacturing purposes only; not for and dacarbazine (ABVD) is considered the standard of treatment human, veterinary, food, or household use. for advanced Hodgkin's lymphoma in North America, providing • This product is offered for R&D use in accordance with (i) 35 a good balance of efficacy and toxicity. Hoskin, P.J. et al., USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese “Randomized comparison of the Stanford V regimen and ABVD Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent in the treatment of advanced Hodgkin's Lymphoma: United Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Kingdom National Cancer Research Institute Lymphoma Group Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) Study ISRCTN 64141244.” J. Clin. Oncol. 27: 5390‑5396 (2009). and other common law exemptions of Canadian patent law; (vi) • Vinblastine chemotherapy is the standard treatment for the Section 68B of the Patents Act of 1953 in New Zealand together patients with aggressive systemic Langerhans cell histiocytosis. with the amendment of same by the Statutes Amendment Bill of Gadner, H. et al., “A randomized trial of treatment for multisystem 2002; (vii) such related legislation and/or case law as may be or Langerhans’ cell histiocytosis.” J. Pediatr. 138: 728‑734 (2001). become applicable in the aforementioned countries; and (viii) such • Vinblastine has potent anti-angiogenic properties at picomolar similar laws and rules as may apply in various other countries. concentrations. The doses of vinblastine needed to cause • Not available in some countries; not available to some institutions; antiangiogenesis are significantly lower than cytotoxic doses. not available for some uses. Vacca, A. et al., “Antiangiogenesis is produced by nontoxic doses of vinblastine.” Blood 94: 4143‑4155 (1999). F • Co-targeting of mTOR by temsirolimus – see Temsirolimus Cl O (Cat. No. T-8040 on page 111) – and microtubules by vinblastine O in vitro resulted in marked growth inhibition in Huh7 cells and N S F Hep3B cells. The combination of temsirolimus and vinblastine CH H O 3 induced a significant and sustained antitumor activity in both N N H Huh7 and Hep3B xenograft models, with significant reduction of tumor vessel density. Zhou, Q. et al., “Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 121 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

vinblastine combination in hepatocellular carcinoma.” Vincrex – see its active ingredient, namely Vincristine, Biochem. Pharmacol. 83: 1146‑1158 (2012). Sulfate Salt (Cat. No. V-8400 on page 122). • Weekly vinblastine was demonstrated to be a reasonable alternative to radiation for pediatric patients with low-grade Vincristine hydrogen sulfate – see Vincristine, Sulfate Salt glioma who had failed first-line chemotherapy. The 5-year (Cat. No. V-8400 on page 122). progression-free survival was shown in this phase II trial to be V-8400 Vincristine, Sulfate Salt, >99% comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. Bouffet, E. et al., “Phase II study of Synonyms: [LCR sulfate] [Leurocristine sulfate] weekly vinblastine in recurrent or refractory pediatric low-grade [Lilly 37231] [22-Oxovincaleukoblastine sulfate] glioma.” J. Clin. Oncol. 30: 1358‑1363 (2012). [VCR sulfate] [Vincristine hydrogen sulfate] • Accelerated methotrexate, vinblastine, doxorubicin, and Related Terms: [Kyocristine] [Marqibo] [Novopharm] cisplatin appeared to be a safe, well-tolerated, and effective [Oncovin] [Onkovin] [Vincasar PFS] [Vincrex] neoadjuvant chemotherapy regimen for muscle-invasive [Vincrisul] bladder cancer. Blick, C. et al., “Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant Size US$ ¤ £ ¥ chemotherapy for patients with muscle-invasive transitional cell 10 mg 38 28 22 4,600 carcinoma of the bladder.” Cancer 118: 3920‑3927 (2012). Prices 25 mg 71 52 42 8,600 • Related CAS number: 865-21-4 for the free base. Reduced! 50 mg 114 84 67 13,800 • STRUCTURE ERRORS ON WIKIPEDIA AND TWO 100 mg 182 134 107 22,000 VENDORS’ WEBSITES: As of December 21, 2012, the 200 mg 325 239 191 39,300 vinblastine structures shown on Wikipedia and at least two vendors’ (Santa Cruz and Sigma) web pages are incorrect in one or 500 mg 515 379 303 62,200 more ways (we have not checked most other vendors’ vinblastine 1 g 922 678 542 111,400 structures). Also, the vinblastine structure shown on Chemblink NOTE: Euro, Pound and Yen prices are revised regularly. fails to specify the stereochemistry at one asymmetric carbon Please visit www.LCLabs.com for our current prices. atom. Finally, the Merck Index Vol. 14 entry for vinblastine shows M.W. 923.04 c46H56N4O10•H2SO4 [2068-78-2] a dashed bond connecting a nitrogen atom and a symmetrically M.I. 14: 9986 substituted carbon atom; this appears to be a bond that would not Storage: Store at or below -20 ºC. Solubility: Soluble normally be shown as embodying stereochemical information, so in DMSO at 60 mg/mL; very poorly soluble in ethanol; our structure shows it as a plain single bond. soluble in water at 25 mg/mL with warming; buffers, • Vinblastine is the active ingredient in drug products sold under serum, or other additives may increase or decrease the numerous trade names, such as those listed near the top of this aqueous solubility. Disposal: A product entry as “Related Terms”. These drug products have been approved in at least one country for use in patients with • Vincristine, also known as leurocristine, sometimes abbreviated cancer. NOTE: THE VINBLASTINE RESEARCH COMPOUND "VCR", is a mitotic inhibitor. SOLD BY LC LABORATORIES IS NOT ANY OF THE • Treatment with cyclophosphamide, hydroxydaunorubicin – see VINBLASTINE-CONTAINING DRUG PRODUCTS SOLD Doxorubicin, Hydrochloride Salt (Cat. No. D-4000 on page UNDER VARIOUS TRADE NAMES AND IS NOT FOR 33) and Doxorubicin, Free Base (Cat. No. D-4099 on page 32), HUMAN USE. Oncovin® (vincristine), and prednisone (CHOP) has long been • Sold for laboratory or manufacturing purposes only; not for the standard therapy for non-Hodgkin's lymphoma. Improvements human, veterinary, food, or household use. have been made to the efficacy of this regimen by increasing the dosing frequency and by adding rituximab immunotherapy to the • This product is offered for R&D use in accordance with (i) 35 regimen. Gisselbrecht, C., “Current approaches to the treatment of USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese non-Hodgkin's lymphoma.” Hematol. Rep. 3: e3 (2011). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) has been the standard of treatment for patients with and other common law exemptions of Canadian patent law; (vi) advanced-stage Hodgkin lymphoma (HL). Kuruvilla, J., Section 68B of the Patents Act of 1953 in New Zealand together “Standard therapy of advanced Hodgkin lymphoma.” with the amendment of same by the Statutes Amendment Bill of Hematology Am. Soc. Hematol. Educ. Program 497‑506 (2009). 2002; (vii) such related legislation and/or case law as may be or • Vincristine was metabolized in vitro more efficiently by become applicable in the aforementioned countries; and (viii) such CYP3A5 than by CYP3A4. In children with precursor B cell similar laws and rules as may apply in various other countries. acute lymphoblastic leukemia, CYP3A5 expressers produced • Not available in some countries; not available to some institutions; more primary metabolite (M1), had lower metabolic ratios of not available for some uses. [vincristine]/[M1], and experienced less vincristine-induced peripheral neuropathy when compared to CYP3A5 non- OH expressers. Egbelakin, A. et al., “Increased risk of vincristine CH N 3 neurotoxicity associated with low CYP3A5 expression H SO . 2 4 genotype in children with acute lymphoblastic leukemia.” H N Pediatr. Blood Cancer 56: 361‑367 (2011). N • Sixty-three patients with advanced chronic lymphocytic leukemia CH H 3 H were treated with vincristine, cyclophosphamide, BCNU, O O O melphalan, and prednisone (M-2 protocol). Complete remission H C O N O 3 CH H O 3 (CR) and partial response (PR) were achieved in 17% and 44%, CH CH OH 3 3 respectively. The median survivals of patients achieving a CR, O CH 3 PR, or no response were 73+, 40, and 14 months, respectively. Kempin, S. et al., “Combination chemotherapy of advanced Vincaleucoblastine sulfate — see Vinblastine, Sulfate Salt chronic lymphocytic leukemia: the M-2 protocol (vincristine, (Cat. No. V-7300 on page 121). BCNU, cyclophosphamide, melphalan, and prednisone).” Vincasar PFS – see its active ingredient, namely Vincristine, Blood 60: 1110‑1121 (1982). Sulfate Salt (Cat. No. V-8400 on page 122). • Exposure of platelets to vincristine resulted in disassembly of microtubules, loss of discoid shape, formation of tubulin crystals, a depressed response to aggregating agents, and reduced secretory

122 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

activity. White, J.G. and Rao, G.H., “Effects of a microtubule stabilizing agent on the response of platelets to vincristine.” V-4050 Vismodegib, Free Base, >99% Blood 60: 474‑483 (1982). Synonyms: [GDC-0449] [HhAntag691] • Vincristine is the active ingredient in the drug sold under the Related Terms: [Erivedge] trade name Oncovin®. This drug is currently approved in at least one country for use to treat patients with cancers in various Size US$ ¤ £ ¥ types of chemotherapy regimens. NOTE: THE VINCRISTINE, 10 mg 39 30 26 4,400 SULFATE SALT RESEARCH COMPOUND SOLD BY 25 mg 55 43 36 6,100 ® LC LABORATORIES IS NOT ONCOVIN AND IS NOT FOR 50 mg 73 56 48 8,200 HUMAN USE. 100 mg 111 86 73 12,400 • Related CAS number: 57-22-7 for the free base. 200 mg 164 127 108 18,300 • We tested the purity of Tocris’ vincristine product, their Cat. No. 500 mg 329 254 218 36,800 1257, Batch 3A, and found HPLC purity of only 82% instead of 1 g 578 447 382 64,600 the claimed 96%. Proton NMR also showed purity lower than 2 g 998 771 660 111,600 claimed. 5 g 1995 1542 1319 223,000 • STRUCTURE ERRORS ON WIKIPEDIA AND FOUR NOTE: Euro, Pound and Yen prices are revised regularly. VENDORS’ WEBSITES: As of December 21, 2012, the Please visit www.LCLabs.com for our current prices. vincristine structures shown on Wikipedia and at least four M.W. 421.30 c H Cl N O S [879085-55-9] vendors’ (Cayman, Santa Cruz, Selleck, and Sigma) web pages are 19 14 2 2 3 incorrect in one or more ways (we have not checked most other Storage: Store at or below -20 ºC. Solubility: Soluble in vendors’ vincristine structures). Also, the vincristine structure DMSO at 200 mg/mL; soluble in ethanol at 10 mg/mL with shown on Chemblink fails to specify the stereochemistry at two warming; very poorly soluble in water; maximum solubility asymmetric carbon atoms. Finally, the Merck Index Vol. 14 in plain water is estimated to be about 10-20 µM; buffers, entry for vincristine shows a dashed bond connecting a nitrogen serum, or other additives may increase or decrease the atom and a symmetrically substituted carbon atom; this appears aqueous solubility. Disposal: A to be a bond that would not normally be shown as embodying • Vismodegib (GDC-0449) is a potent hedgehog (Hh) signaling stereochemical information, so our structure shows it as a plain pathway inhibitor. single bond. • The overexpression of ATP-binding cassette (ABC) transporters • Vincristine is the active ingredient in drug products sold under is associated with multidrug resistance. Vismodegib is a numerous trade names, such as those listed near the top of this potent inhibitor of two ABC transporters, ABCG2/BCRP and product entry as "Related Terms". These drug products have ABCB1/Pgp, with IC50 values of 1.4 and 3.0 µM, respectively. been approved in at least one country for use in patients with Zhang, Y. et al., “Hedgehog pathway inhibitor HhAntag691 cancer. NOTE: THE VINCRISTINE RESEARCH COMPOUND is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp.” SOLD BY LC LABORATORIES IS NOT ANY OF THE Neoplasia 11: 96‑101 (2009). VINCRISTINE-CONTAINING DRUG PRODUCTS SOLD • A phase 1 clinical trial demonstrated that vismodegib had UNDER VARIOUS TRADE NAMES AND IS NOT FOR antitumor activity in locally advanced or metastatic basal- HUMAN USE. cell carcinoma. Von Hoff, D.D. et al., “Inhibition of the • Sold for laboratory or manufacturing purposes only; not for hedgehog pathway in advanced basal-cell carcinoma.” human, veterinary, food, or household use. N. Engl. J. Med. 361: 1164‑1172 (2009). • This product is offered for R&D use in accordance with (i) 35 • The treatment with vismodegib of a 26-year-old man with USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese metastatic medulloblastoma that was refractory to multiple Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent therapies resulted in rapid but transient regression of the tumor Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. and relief of symptoms. Rudin, C.M. et al., “Treatment of Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) medulloblastoma with hedgehog pathway inhibitor GDC-0449.” and other common law exemptions of Canadian patent law; (vi) N. Engl. J. Med. 361: 1173‑1178 (2009). Section 68B of the Patents Act of 1953 in New Zealand together • Vismodegib at doses as low as 12.5 mg/kg BID caused complete with the amendment of same by the Statutes Amendment Bill of tumor regression in a medulloblastoma allograft mouse model 2002; (vii) such related legislation and/or case law as may be or which is dependent on the Hh pathway for growth. Robarge, K.D. become applicable in the aforementioned countries; and (viii) such et al., “GDC-0449-a potent inhibitor of the hedgehog pathway.” similar laws and rules as may apply in various other countries. Bioorg. Med. Chem. Lett. 19: 5576‑5581 (2009). • Not available in some countries; not available to some institutions; • Acquired mutations in Smoothened (SMO), a serpentine receptor, not available for some uses. inhibited the ability of vismodegib to bind SMO and served as a OH mechanism of drug resistance in human cancer. Yauch, R.L. et al., CH N 3 “Smoothened mutation confers resistance to a Hedgehog pathway H SO . 2 4 inhibitor in medulloblastoma.” Science 326: 5576‑5581 (2009). H N • Sold for laboratory or manufacturing purposes only; not for N human, medical, veterinary, food, or household use. CH H 3 H • This product is offered for R&D use in accordance with (i) 35 O O O H C O N O USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese 3 CH H O 3 CH Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent 3 OH H O O Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. CH 3 Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Vincrisul – see its active ingredient, namely Vincristine, Section 68B of the Patents Act of 1953 in New Zealand together Sulfate Salt (Cat. No. V-8400 on page 122). with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; not available for some uses.

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 123 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

Cl • Not available in some countries; not available to some institutions; O Cl not available for some uses. N N H O O H N OH S N CH 3 O O H VLB sulfate — see Vinblastine, Sulfate Salt (Cat. No. V-7300 on page 121). Votrient — see its active ingredient,V-8477 namely Pazopanib, Free Base (Cat. No. P-6706 on page 81). V-8477 Vorinostat, >99% VP-16 — see Etoposide (Cat. No. E-4488 on page 38) and Etoposide [SAHA] [Suberanilohydroxamic Acid] 4'-Phosphate, Free Acid (Cat. No. E-4444 on page 39). [Suberoylanilide Hydroxamic Acid] [Zolinza] VP-16-213V-8477 —2010-02-12 see Etoposid HZ_RevSKC.skce (Cat. No. E-4488 on page 38) Size US$ ¤ £ ¥ and Etoposide 4'-Phosphate, Free Acid (Cat. No. E-4444 on page 39). 250 mg 41 32 27 4,600 500 mg 72 56 48 8,000 VX-680 – see Tozasertib, Free Base (Cat. No. T-2304 on page 116). 1 g 121 94 80 13,500 V-9366 VX-702, >99% 2 g 214 165 141 23,900 5 g 475 367 314 53,100 Size US$ ¤ £ ¥ 10 g 840 649 555 93,900 10 mg 34 26 22 3,400 25 g 1670 1291 1104 186,700 25 mg 75 57 49 7,500 NOTE: Euro, Pound and Yen prices are revised regularly. 50 mg 129 99 85 12,800 Please visit www.LCLabs.com for our current prices. 100 mg 215 165 141 21,400 M.W. 264.32 c14H20N2O3 [149647-78-9] 200 mg 398 305 261 39,600 Storage: Store at or below -20 ºC. Solubility: Soluble in 1 g 1495 1145 981 148,700 DMSO at 66 mg/mL; soluble in ethanol at 2 mg/mL with NOTE: Euro, Pound and Yen prices are revised regularly. slight warming; very poorly soluble in water; maximum Please visit www.LCLabs.com for our current prices. solubility in plain water is estimated to be about 20‑50 µM; M.W. 404.32 c H F N O [745833-23-2] buffers, serum, or other additives may increase or 19 12 4 4 2 decrease the aqueous solubility. Disposal: A Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A • Vorinostat is a histone deacetylase inhibitor and causes growth arrest and death of some transformed cells both in vitro and • VX-702 is a second-generation, orally active mitogen-activated in vivo, with little or no toxic effects on normal cells. Marks, P.A., protein kinase (MAPK) p38 inhibitor. It is being tested for the “Discovery and development of SAHA as an anticancer agent.” potential treatment of inflammation, rheumatoid arthritis and Oncogene 26: 1351‑1356 (2007). cardiovascular diseases. Ding, C., “Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary • Vorinostat was studied in single agent trials and combination trials syndrome.” Curr. Opin. Investig. Drugs 7: 1020‑1025 (2006). for patients with refractory cutaneous T cell lymphoma. Cang, S. et al., “New clinical developments in histone deacetylase inhibitors • p38 MAPK increases thromboxane levels by activating for epigenetic therapy of cancer.” J. Hematol. Oncol. 2: 22 (2009). phospholipase A2, thus catalyzing the formation of arachidonic acid. VX-702 inhibited activation of p38 MAPK by thrombin, • Vorinostat caused an accumulation of acetylated histones, SFLLRN, AYPGKF and U46619 in platelets. Kuliopulos, A. et al., p21(WAF1) and bax, a decrease of Stat6, and activation of “Effect of selective inhibition of the p38 MAP kinase pathway on caspase-3 , and thus selectively induced malignant T cell platelet aggregation.” Thromb. Haemost. 92: 1387‑1393 (2004). apoptosis. Zhang, C. et al., “Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell • VX-702 showed modest clinical efficacy and transient lymphoma cells: relevance to mechanism of therapeutic action.” suppression of biomarkers of inflammation in patients J. Invest. Dermatol. 125: 1045‑1052 (2005). with rheumatoid arthritis. Damjanov, N. et al., “Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 • Vorinostat improves tumor radioresponse. Munshi, A. et al., MAPK inhibitor, in rheumatoid arthritis: results of two “Vorinostat, a histone deacetylase inhibitor, enhances the response randomized, double-blind, placebo-controlled clinical studies.” of human tumor cells to ionizing radiation through prolongation of Arthritis Rheum. 60: 1232‑1241 (2009). gamma-H2AX foci.” Mol. Cancer Ther. 5: 1967‑1974 (2006). • Another CAS number previously assigned to VX-702, • Vorinostat is the active ingredient in the drug sold under the 479543‑46‑9, has been deleted by CAS and is no longer in use. trade name Zolinza®. The drug is currently approved in at least one country for use in patients with cutaneous T cell lymphoma • Sold for laboratory or manufacturing purposes only; not for (CTCL) and Sézary syndrome, another type of lymphoma closely human, medical, veterinary, food, or household use. related to CTCL. NOTE: The vorinostat product sold by LC • This product is offered for R&D use in accordance with (i) 35 Laboratories is NOT Zolinza® and is NOT for human use. USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese • Sold for laboratory or manufacturing purposes only; not for Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent human, medical, veterinary, food, or household use. Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) • This product is offered for R&D use in accordance with (i) 35 and other common law exemptions of Canadian patent law; (vi) USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Section 68B of the Patents Act of 1953 in New Zealand together Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent with the amendment of same by the Statutes Amendment Bill of Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. 2002; (vii) such related legislation and/or case law as may be or Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) become applicable in the aforementioned countries; and (viii) such and other common law exemptions of Canadian patent law; (vi) similar laws and rules as may apply in various other countries. Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of • Not available in some countries; not available to some institutions; 2002; (vii) such related legislation and/or case law as may be or not available for some uses. become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.

124 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

O • Wortmannin inhibition of PI3-K also blocks many of the short- F term metabolic effects induced by insulin receptor activation NH 2 in isolated rat adipocytes without affecting the insulin receptor tyrosine kinase activity. Okada, T. et al., “Essential role of NN phosphatidylinositol 3-kinase in insulin-induced glucose transport F ONH F F and antilipolysis in rat adipocytes. Studies with a selective 2 inhibitor wortmannin.” J. Biol. Chem. 269: 3568‑3573 (1994). VX6 – see Tozasertib, Free Base (Cat. No. T-2304 on page 116). Moule, S.K. and Denton, R.M., “Multiple signaling pathways involved in the metabolic effects of insulin.” W-2990 Wortmannin, >99% Am. J. Cardiol. 80: 41A‑49A (1997). [KY 12420] • Inhibits platelet activating factor-induced MAP kinase activation in guinea pig neutrophils (200 - 300 nM). Ferby, I.M. et al., SizeV-9366-2009-10-17-kedREV.SKC US$ ¤ £ ¥ “Wortmannin inhibits mitogen-activated protein kinase 10 mg 27 22 17 2,100 activation induced by platelet-activating factor in guinea pig 25 mg 59 47 37 4,600 neutrophils.” J. Biol. Chem. 269: 30485‑30488 (1994). 50 mg 111 88 70 8,700 • Inhibits phospholipase D activation. Bonser, R.W. 100 mg 206 164 130 16,200 et al., “Demethoxyviridin and wortmannin block phospholipase C and D activation in the human neutrophil.” 300 mg 525 418 332 41,200 Br. J. Pharmacol. 103: 1237‑1241 (1991). 500 mg 845 673 534 66,300 • Sold for laboratory or manufacturing purposes only; not for 1 g 1635 1303 1033 128,300 human, medical, veterinary, food, or household use. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. O O M.W. 428.43 c23H24O8 [19545-26-7] M.I. 14: 10053 O O Storage: Store at or below -20 ºC. Solubility: Soluble in O DMSO or ethanol; very poorly soluble in water; maximum H solubility in plain water is estimated to be about 10‑50 µM; O O buffers, serum or other additives may increase or decrease the aqueous solubility. Disposal: A O • Isolated from the filamentous fungus, Penicillium funiculosum, Xabine – see Capecitabine (Cat. No. C-2799 on page 17). wortmannin is a potent, irreversible, and specific inhibitor of phosphatidylinositol 3-kinase (PI3-K) with an IC of Xalkori – see its active ingredient, namely Crizotinib, Free Base 50 (Cat. No. C-7900 on page 23). 2-5 nM. Arcaro, A. and Wymann, M.P., “Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of Xeljanz – see Tofacitinib, Free Base (Cat. No. T-1377 on page 114) phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses.” and its active ingredient, namely Tofacitinib, Citrate Salt Biochem. J. 296: 297‑301 (1993). Wymann, M.P. and Arcaro, A., (Cat. No. T-1399 on page 115). “Platelet-derived growth factor-induced phosphatidylinositol 3-kinase activation mediates actin rearrangements in fibroblasts.” Xeloda – see its active ingredient, namely Capecitabine (Cat. No. C-2799 on page 17). Biochem. J. 298: 517‑520 (1994). Powis, G. et al., “Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3- XL-880 — see Foretinib, Free Base (Cat. No. F-4185 on page 43). kinase.” Cancer Res. 54: 2419‑2423 (1994). Wymann, M.P. et al., “Wortmannin inactivates phosphoinositide 3-kinase by covalent XRP-6258 — see Cabazitaxel (Cat. No. C-2581 on page 15). modification of Lys-802, a residue involved in the phosphate Y-5399 Y-27632, Free Base, >99% transfer reaction.” Mol. Cell Biol. 16: 1722‑1733 (1996). Synonyms: [Y27] • Inhibitor of both myosin light chain kinase (IC50 = 200 nM) and phosphatidylinositol 4-kinase at concentrations approximately Size US$ ¤ £ ¥ 100-fold higher than the that required for PI3-K inhibition. Nakanishi, S. et al., “Wortmannin, a microbial product inhibitor of 5 mg 49 35 29 5,600 myosin light chain kinase.” J. Biol. Chem. 267: 2157‑2163 (1992). New! 10 mg 81 58 49 9,200 • Enhances radiation- or serum withdrawal-induced apoptosis 25 mg 188 135 113 21,400 through the inhibition of PI3-K/Akt signal transduction 50 mg 335 241 201 38,100 cascade and blocks the antiapoptotic effect of cytokines. 100 mg 615 442 369 69,900 Krasilnikov, M. et al., “Contribution of phosphatidylinositol 200 mg 1170 841 703 132,900 3-kinase to radiation resistance in human melanoma cells.” 250 mg 1375 988 826 156,200 Mol. Carcinog. 24: 64‑69 (1999). Allen, M.P. et al., “Growth NOTE: Euro, Pound and Yen prices are revised regularly. arrest-specific gene 6/adhesion related kinase signaling Please visit www.LCLabs.com for our current prices. promotes gonadotropin-releasing hormone neuronal survival M.W. 247.34 C H N O [146986-50-7] via extracellular signal-regulated kinase (ERK) and Akt.” 14 21 3 Mol. Endocrinol. 13: 191‑201 (1999). Morita, Y. et al., Storage: Store at or below -20 ºC. Solubility: Soluble in “Requirement for phosphatidylinositol-3'-kinase in cytokine- DMSO. Disposal: A mediated germ cell survival during fetal oogenesis in the • This research compound is the free base form of Y-27632; see the mouse.” Endocrinology 140: 941‑949 (1999). Manna, S.K. salt form of this product (Y-27632, Dihydrochloride Salt, Cat. No. and Aggarwal, B.B., “Interleukin-4 down-regulates both Y-5301 on page 126) for further technical information about both of forms of tumor necrosis factor receptor and receptor-mediated these research compounds. apoptosis, NFkappaB, AP-1, and c-Jun N-terminal kinase.” • This Y-27632 product is the free base form, whose CAS number is J. Biol. Chem. 273: 33333‑33341 (1998). Crowder, R.J. given above. The CAS number of the dihydrochloride salt form is and Freeman, R.S., “Phosphatidylinositol 3-kinase and Akt 129830-38-2. protein kinase are necessary and sufficient for the survival • Related CAS number: 331752-47-7 for Y-27632 diHCl salt of nerve growth factor-dependent sympathetic neurons.” monohydrate. J. Neurosci. 18: 2933‑2943 (1998).

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 125 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

• A CAS number previously assigned to Y-27632 diHCl salt rat models. Uehata, M. et al., "Calcium sensitization of monohydrate, namely 203911-23-3, has been deleted by CAS smooth muscle mediated by a Rho-associated protein kinase in and is no longer in use, and a CAS number previously assigned to hypertension." Nature 389: 990‑994 (1997). Y-27632, Free Base, namely 742043-06-7, has also been deleted • Y-27632 inhibited cell transformation mediated by RhoA and by CAS and is also no longer in use. its guanine-nucleotide exchange factor (GEF). Sahai, E. et al., • As of October 2013, many other vendors (Adipogen, Affix, "Transformation mediated by RhoA requires activity of ROCK AG Scientific, BioVision, Calbiochem/EMD, Cellagen, Enzo, kinases." Curr. Biol. 9: 136‑145 (1999). MyBioSource, Reagents Direct, Santa Cruz, VDM Biochemicals, • Y-27632 inhibited both Rho-mediated activation of actomyosin etc.) are incorrectly using CAS number 146986-50-7 for the diHCl and invasive activity of rat MM1 hepatoma cells. Continuous or diHCl monohydrate salt forms of Y-27632. Chemical Abstracts delivery of Y-27632 largely prevented the dissemination Service has assigned the CAS number 146986-50-7 to the free of MM1 cells implanted into the peritoneal cavity of base form only. syngeneic rats. Itoh, K. et al., "An essential part for Rho- • Sold for laboratory or manufacturing purposes only; not for associated kinase in the transcellular invasion of tumor cells." human, veterinary, food, or household use. Nat. Med. 5: 221‑225 (1999). • This product is offered for R&D use in accordance with (i) 35 • Y-27632 blocked chemotactic peptide-induced development of USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese cell polarity and locomotion, and inhibited myosin light chain Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent phosphorylation with similar potency (ED50 = 0.5‑1.1 µM). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Niggli, V., "Rho-kinase in human neutrophils: a role in signalling Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) for myosin light chain phosphorylation and cell migration." and other common law exemptions of Canadian patent law; (vi) FEBS Lett. 445: 69‑72 (1999). Section 68B of the Patents Act of 1953 in New Zealand together • Y-27632 had antinociceptive properties, possibly by with the amendment of same by the Statutes Amendment Bill of inhibition of Rho-kinase. Buyukafsar, K. et al., "Rho-kinase 2002; (vii) such related legislation and/or case law as may be or inhibitor, Y-27632, has an antinociceptive effect in mice." become applicable in the aforementioned countries; and (viii) such Eur. J. Pharmacol. 541: 49‑52 (2006). similar laws and rules as may apply in various other countries. • Y-27632 blocked the development of ischemia/reperfusion- • Not available in some countries; not available to some institutions; induced acute renal failure, possibly by inhibiting not available for some uses. myeloperoxidase activity in an early phase after reperfusion. Teraishi, K. et al., "Preventive effect of Y-27632, a selective N O Rho-kinase inhibitor, on ischemia/reperfusion-induced acute renal N failure in rats." Eur. J. Pharmacol. 505: 205‑211 (2004). H CH • Y-27632 prevented intrahepatic metastasis of human hepatocellular 3 H carcinoma. Takamura, M. et al., "Inhibition of intrahepatic NH 2 metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632." Hepatology 33: 577‑581 (2001). Y-5301 Y-27632, Dihydrochloride Salt, >99% • Y-27632 inhibited both of lysophosphatidic acid (LPA)- and Synonyms: [Y27] fibronectin (FN)-induced migration and morphological change of rat ascites hepatoma (MM1) cells. It impaired LPA- and Size US$ ¤ £ ¥ FN-evoked formation of focal adhesions and actin bundles and 5 mg 49 35 29 5,600 suppressed LPA- and FN-induced tyrosine phosphorylation of 10 mg 81 58 49 9,200 focal adhesion kinase and paxillin in MM1 cells. Imamura, F. New! et al., "Y-27632, an inhibitor of rho-associated protein kinase, 25 mg 188 135 113 21,400 suppresses tumor cell invasion via regulation of focal adhesion and 50 mg 335 241 201 38,100 focal adhesion kinase." Jpn. J. Cancer Res. 91: 811‑816 (2000). 100 mg 442 369 69,900 615 • This Y-27632 product is the dihydrochloride salt, whose CAS 200 mg 1170 841 703 132,900 number is given above. The CAS number of the free base form is 250 mg 1375 988 826 156,200 146986-50-7. NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. • Related CAS number: 331752-47-7 for Y-27632 diHCl salt monohydrate. M.W. 320.26 c H N O•2HCl [129830-38-2] 14 21 3 • A CAS number previously assigned to Y-27632 diHCl salt Storage: Store at or below -20 ºC. Solubility: Soluble in monohydrate, namely 203911-23-3, has been deleted by CAS DMSO at 160 mg/mL; soluble in ethanol at 12 mg/mL with and is no longer in use, and a CAS number previously assigned to warming; soluble in water at 90 mg/mL; buffers, serum, Y-27632, Free Base, namely 742043-06-7, also has been deleted or other additives may increase or decrease the aqueous by CAS and is also no longer in use. solubility. Disposal: A • As of October 2013, many other vendors (Adipogen, Affix, • Y-27632 is a novel and specific Rho-associated coiled-coil AG Scientific, BioVision, Calbiochem/EMD, Cellagen, Enzo, forming protein kinase (ROCK) inhibitor. Narumiya, S. et al., MyBioSource, Reagents Direct, Santa Cruz, VDM Biochemicals, "Use and properties of ROCK-specific inhibitor Y-27632." etc.) are incorrectly using CAS number 146986-50-7 for the diHCl Methods Enzymol. 325: 273‑284 (2000). or diHCl monohydrate salt forms of Y-27632. Chemical Abstracts • This research compound is the dihydrochloride salt form of Service has assigned the CAS number 146986-50-7 to the free Y-27632. We also offer the free base form (see Y-27632, base form only. Free Base, Cat. No. Y-5399 on page 125). • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • Y-27632 inhibited ROCK-I (Ki = 0.22 µM) and ROCK-II (Ki = 0.30 µM) by competing with ATP for its binding to • This product is offered for R&D use in accordance with (i) 35 the kinase. Ishizaki, T. et al., "Pharmacological properties USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese of Y-27632, a specific inhibitor of rho-associated kinases." Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Mol. Pharmacol. 57: 976‑983 (2000). Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. • Y-27632 selectively inhibited Ca2+ sensitization of smooth Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) muscle and blocked its contraction, prevented Rho-induced, and other common law exemptions of Canadian patent law; (vi) p160ROCK-mediated formation of stress fibers in cultured cells, Section 68B of the Patents Act of 1953 in New Zealand together and dramatically lowered hypertension in several hypertensive with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or

126 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. Z-9900 Z-VAD-FMK, Methyl Ester, >99% • Not available in some countries; not available to some institutions; Synonyms: [Benzyloxycarbonyl-Val-Ala-Asp(OMe)- not available for some uses. fluoromethylketone] [Z-VAD(OMe)-FMK] [Z-Val-Ala- Asp(OMe)-FMK] [Z-Val-Ala-Asp-FMK, Methyl Ester] N O Size US$ ¤ £ ¥ N H 1 mg 49 38 32 5,500 CH 3 . 2HCl 5 mg 185 143 122 20,700 H NH 10 mg 275 213 182 30,700 2 25 mg 588 455 389 65,700 Y27 – see Y-27632, Free Base (Cat. No. Y-5399 on page 125) and 100 mg 997 771 659 111,500 Y-27632, Dihydrochloride Salt (Cat. No. Y-5301 on page 126). NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. YM-177 – see Celecoxib (Cat. No. C-1502 on page 20). M.W. 467.49 C22H30FN3O7 [187389-52-2] YM155 – see Sepantronium Bromide (Cat. No. S-7272 on page 104). Storage: Store at or below -20 ºC. Solubility: Soluble in Z-Riboside – see AICAR, Free Base (Cat. No. A-1098 on page 5). DMSO. Disposal: A Z-VAD(OMe)-FMK – see Z-VAD-FMK, Methyl Ester • Z-VAD-FMK is a caspase inhibitor and antiapoptotic agent. (Cat. No. Z-9900 on page 127). • The apoptotic responses of human melanocytes to UV radiation, 4-tert-butylphenol, and cisplatin were associated with BH3 Z-9999 Z-VAD-FMK, Free Acid, >99% interacting domain cleavage, caspase activation, mitochondrial Synonyms: [Benzyloxycarbonyl-Val-Ala-Asp- depolarization and release of cytochrome c, Smac/DIABLO, fluoromethylketone] [Caspase Inhibitor VI] [Z-Val-Ala- and apoptosis-inducing factor (AIF), but not endonuclease G. Asp-FMK] Z‑VAD‑FMK was not able to block these apoptotic responses and AIF release, indicating that the apoptotic responses were Size US$ ¤ £ ¥ caspase-independent. Liu, T. et al., “Activation of dual apoptotic 1 mg 49 38 32 5,500 pathways in human melanocytes and protection by survivin.” J. Invest. Dermatol. 126: 2247‑2256 (2006). 5 mg 185 143 122 20,700 10 mg 275 213 182 30,700 • Z‑VAD‑FMK decreased TNF-induced enterocyte detachment and apoptosis as well as villus atrophy in mice. Piguet, P.F. et al., 25 mg 588 455 389 65,700 “TNF-induced enterocyte apoptosis and detachment in mice: 100 mg 997 771 659 111,500 induction of caspases and prevention by a caspase inhibitor, NOTE: Euro, Pound and Yen prices are revised regularly. ZVAD-fmk.” Lab. Invest. 79: 495‑500 (1999). Please visit www.LCLabs.com for our current prices. • Z‑VAD‑FMK up-regulated caspase-9 activity, which was M.W. 453.46 c21H28FN3O7 [161401-82-7] involved in an amplification loop of etoposide-induced Storage: Store at or below -20 ºC. Solubility: Soluble in cell death at the mitochondrial level in mouse embryonic DMSO. Disposal: A fibroblasts. Rodríguez‑Enfedaque, A. et al., “zVAD-fmk • This Z‑VAD‑FMK product is the free acid form. Please see the upregulates caspase-9 cleavage and activity in etoposide- other form of this product, Z-VAD-FMK, Methyl Ester (Cat. No. induced cell death of mouse embryonic fibroblasts.” Z-9900 on page 127), for further technical information about both of Biochim. Biophys. Acta. 1823: 1343‑1352 (2012). these products. • Z‑VAD‑FMK increased cisplatin-induced renal • Related CAS number: 187389-52-2 for the aspartyl methyl ester, damage. Herzog, C. et al., “zVAD-fmk prevents and 220644-02-0, in which the stereochemistry at the aspartyl cisplatin-induced cleavage of autophagy proteins but alpha position is not specified. impairs autophagic flux and worsens renal function.” Am. J. Physiol. Renal. Physiol. 303: F1239‑F1250 (2012). • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use. • This Z‑VAD‑FMK product is the methyl ester. We also offer the free acid form – see Z-VAD-FMK, Free Acid (Cat. No. Z-9999 on • This product is offered for R&D use in accordance with (i) 35 page 127). USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent • Related CAS numbers: 161401-82-7 for the aspartyl free acid Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. form, and 634911-81-2, where the stereochemistry at the aspartyl Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) alpha position is not specified. and other common law exemptions of Canadian patent law; (vi) • Another CAS number previously assigned to Z-VAD-FMK methyl Section 68B of the Patents Act of 1953 in New Zealand together ester, namely 211292-24-9, has been deleted by CAS and is no with the amendment of same by the Statutes Amendment Bill of longer in use. 2002; (vii) such related legislation and/or case law as may be or • STRUCTURE ERROR: As of December 21, 2012, the PDF become applicable in the aforementioned countries; and (viii) such structure reached from a link on Calbiochem's web page for this similar laws and rules as may apply in various other countries. product erroneously shows the free acid compound rather than • Not available in some countries; not available to some institutions; the methyl ester compound. Calbiochem’s product page itself not available for some uses. correctly shows the ester compound – only the PDF structure reached via the link is incorrect (we have not checked most other O vendors’ Z-VAD-FMK acid or ester structures). H C CH 3 3 O H O OH • Sold for laboratory or manufacturing purposes only; not for s N human, veterinary, food, or household use. s O N s N F H • This product is offered for R&D use in accordance with (i) 35 H O CH H O 3 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 127 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com

with the amendment of same by the Statutes Amendment Bill of cells and reduced potential for systemic immunosuppression.” 2002; (vii) such related legislation and/or case law as may be or J. Cardiovasc. Pharmacol. 49: 228‑235 (2007). become applicable in the aforementioned countries; and (viii) such • In vitro, zotarolimus inhibited FKBP-12 binding (IC = 2.8 similar laws and rules as may apply in various other countries. 50 nM) and potently blocked smooth muscle cell (IC50 = 2.9 nM) • Not available in some countries; not available to some institutions; and endothelial cell (IC50 = 2.6 nM) proliferation. After 28 days, not available for some uses. zotarolimus stents from domestic juvenile swine exhibited less

O area stenosis (22.4% vs. 35.7%), less neointimal area (1.69 vs. 2.78 mm2), less neointimal thickness (0.25 vs. 0.38 mm), H C CH CH 3 3 3 2 O H O O and greater lumen area (6.07 vs. 5.02 mm ) when compared s N to phosphorylcholine-coated stents. Garcia-Touchard, A. s O N s N F H et al., “Zotarolimus-eluting stents reduce experimental H O CH H O 3 coronary artery neointimal hyperplasia after 4 weeks.” Eur. Heart J. 27: 988‑993 (2006). Z-Val-Ala-Asp(OMe)-FMK – see Z-VAD-FMK, Methyl Ester • Zotarolimus was also designed for use in stents that have (Cat. No. Z-9900 on page 127). phosphorylcholine as a carrier. Z-Val-Ala-Asp-FMK – see Z-VAD-FMK, Free Acid • Zotarolimus is the active drug in the drug-eluting stents sold under (Cat. No. Z-9999 on page 127). the trade names Endeavor® and ZoMaxx®. NOTE: the zotarolimus sold by LC Laboratories is NOT Endeavor® nor ZoMaxx® and is Z-Val-Ala-Asp-FMK, Methyl Ester – see Z-VAD-FMK, Methyl Ester NOT for human use. (Cat. No. Z-9900 on page 127). • Sold for laboratory or manufacturing purposes only; not for Zactima – see its active ingredient, namely Vandetanib, Free Base human, medical, veterinary, food, or household use. (Cat. No. V-9402 on page 119). • This product is offered for R&D use in accordance with (i) 35 Zarnestra – see its active ingredient, namely Tipifarnib, Free Base USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese (Cat. No. T-9104 on page 112). Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. ZD1839 – see Gefitinib, Free Base (Cat. No. G-4408 on page 45). Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) ZD6474 – see Vandetanib, Free Base (Cat. No. V-9402 on page 119). and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together Zefei — see Gemcitabine, Free Base (Cat. No. G-4199 on page 46) with the amendment of same by the Statutes Amendment Bill of and its active ingredient, namely Gemcitabine, Hydrochloride 2002; (vii) such related legislation and/or case law as may be or Salt (Cat. No. G-4177 on page 47). become applicable in the aforementioned countries; and (viii) such Zelboraf — see its active ingredient, namely Vemurafenib, similar laws and rules as may apply in various other countries. Free Base (Cat. No. V-2800 on page 120). • Not available in some countries; not available to some institutions; not available for some uses. ZK 222584 – see Vatalanib, Dihydrochloride Salt (Cat. No. V-8303 on page 120). N N N ZK-62711 – see (R,S)-Rolipram (Cat. No. R-2020 on page 98). N Zolinza – see its active ingredient, namely Vorinostat CH O 3 CH (Cat. No. V-8477 on page 124). 3 ZoMaxx – see its active ingredient, namely Zotarolimus, Free Base H (Cat. No. Z-9040 on page 128). O O OH N H Zortress – see Everolimus (Cat. No. E-4040 on page 40). O O O CH O O 3 Z-9040 Zotarolimus, Free Base, >98% HO O OCH Synonyms: [ABT-578] 3 [40-epi-(N1-Tetrazolyl)-rapamycin] Related Terms: [Endeavor] [ZoMaxx] (Please inquire for availability or visit www.lclabs.com) Z-1066 ZSTK474, Free Base, >99%

Size US$ ¤ £ ¥ Size US$ ¤ £ ¥ 5 mg 148 111 94 13,700 25 mg 32 24 21 2,500 25 mg 335 251 212 31,100 50 mg 43 32 28 3,400 100 mg 685 513 434 63,500 100 mg 75 56 48 5,900 250 mg 1240 928 785 115,000 200 mg 138 103 88 10,800 500 mg 2240 1676 1418 207,700 250 mg 159 119 102 12,400 NOTE: Euro, Pound and Yen prices are revised regularly. 1 g 314 234 201 24,500 Please visit www.LCLabs.com for our current prices. 2 g 584 436 374 45,600 M.W. 966.21 c52H79N5O12 [221877-54-9] NOTE: Euro, Pound and Yen prices are revised regularly. Please visit www.LCLabs.com for our current prices. Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A M.W. 417.41 C19H21F2N7O2 [475110-96-4] • Zotarolimus (also known as ABT-578) is an analogue of Storage: Store at or below -20 ºC. Solubility: Soluble in rapamycin (sirolimus) that was designed to have a shorter in DMSO at 20 mg/mL; soluble in ethanol at 2.5 mg/mL with vivo half-life than rapamycin. Zotarolimus was found to be warming; very poorly soluble in water; maximum solubility comparable in potency for inhibiting in vitro proliferation of both in plain water is estimated to be about 1-5 µM; buffers, rat and human T cells and mechanistically similar to sirolimus serum, or other additives may increase or decrease the in having high-affinity binding to the immunophilin FKBP12. aqueous solubility. Disposal: A Chen, Y.W. et al., “Zotarolimus, a novel sirolimus analogue with • ZSTK474, a novel s-triazine derivative, binds to the ATP- potent anti-proliferative activity on coronary smooth muscle binding site of Class I phosphatidylinositol 3-kinases (PI3K) and

128 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT In Business for 34 Years – Since 1980

inhibits PI3K activity. ZSTK474 has strong antitumor activities against human cancer xenografts (A549, PC-3 and WiDr) when administered orally to mice. Furthermore, ZSTK474 did not show significant toxicity at the doses tested. Yaguchi, S. et al., “Antitumor Activity of ZSTK474, a New Phosphatidylinositol 3-Kinase Inhibitor. J Natl. Cancer Inst. 98: 545‑556 (2006). • The Class I PI3K inhibitory activity of ZSTK474 is not isoform- specific within the class — it is an ATP-competitive inhibitor of all four Class I PI3K isoforms. However, ZSTK474 inhibits PI3Kδ most potently, with a Ki of 1.8 nM, while it inhibits the α, β and γ isoforms at slightly higher concentrations (6.7 nM, 10.4 nM and 11.7 nM, respectively). Kong, D. and Yamori, T., “ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms.” Cancer Sci. 98: 1638‑1642 (2007). • ZSTK474 is a far more potent Class I PI3K inhibitor than LY294002, by a factor of 30-fold or more, and it is far more stable than wortmannin. Kong, D. and Yamori, T., ibid. • ZSTK474 is also less toxic than LY 294002 and wortmannin in animal model tests. Yaguchi, S. et al., op. cit. • Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use. • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries. • Not available in some countries; not available to some institutions; not available for some uses.

O

N

F N N F

N N N N O

Zuyeyidal — see its active ingredient, namely Etoposide (Cat. No. E‑4488 on page 38) and Etoposide 4'‑Phosphate, Free Acid (Cat. No. E‑4444 on page 39). Z-1066-2008-10-22-kedRev.skc End of File

WE ACCEPT MC®, VISA®, JBC, AMERICAN EXPRESS® SEE PAGE iv FOR DISPOSAL CODE EXPLANATIONS 129 LC Laboratories® Tel: (800) 937-3720 Fax: (781) 938-5420 www.LCLabs.com Notes:

130 PLEASE INQUIRE FOR BULK QUANTITIES OF ANY LISTED PRODUCT Catalog Number Index

A-1040...... 7 E-4444...... 39 M-2433...... 69 R-6712...... 97 A-1088...... 8 E-4488...... 38 M-2900...... 69 R-7040...... 97 A-1098...... 5 E-4506...... 34 M-2999...... 70 R-7117...... 98 A-1107...... 7 E-4997...... 37 M-4620...... 68 R-8765...... 97 A-1803...... 1 E-5500...... 36 M-5602...... 71 R-9630...... 99 A-2345...... 8 E-5880...... 37 M-6730...... 67 S-1700...... 102 A-3000...... 3 E-8000...... 35 M-7007...... 68 S-2440...... 109 A-3465...... 6 F-4077...... 41 M-8090...... 67 S-3400...... 103 A-6880...... 1 F-4185...... 43 N-4288...... 75 S-4490...... 104 A-6900...... 2 F-4633...... 42 N-5300...... 74 S-5100...... 103 A-7860...... 3 F-4660...... 40 N-6404...... 71 S-7272...... 104 A-8644...... 4 F-4900...... 42 N-8207...... 72 S-7979...... 107 B-1080...... 9 F-9929...... 44 N-9055...... 73 S-8502...... 106 B-1408...... 11 G-1152...... 49 N-9077...... 72 S-8599...... 105 B-1709...... 12 G-2822...... 50 O-1666...... 76 S-8803...... 110 B-1722...... 13 G-4177...... 46 O-2220...... 76 S-8877...... 109 B-1788...... 12 G-4199...... 46 O-3077...... 75 S-8906...... 102 B-2422...... 10 G-4408...... 45 O-5679...... 78 S-9033...... 101 B-3517...... 15 G-4500...... 46 O-5857...... 77 S-9300...... 108 B-6697...... 15 G-4789...... 51 O-7111...... 79 S-9344...... 108 B-7100...... 10 G-5200...... 49 O-7519...... 77 T-1377...... 114 B-8500...... 14 G-5903...... 51 O-9201...... 78 T-1399...... 115 C-1201...... 17 G-6055...... 48 P-1010...... 86 T-2304...... 116 C-1502...... 20 G-6203...... 50 P-1680...... 87 T-3250...... 112 C-1999...... 22 G-9252...... 44 P-2170...... 86 T-5096...... 112 C-2581...... 15 H-2330...... 52 P-3333...... 82 T-6466...... 113 C-2606...... 21 H-5239...... 52 P-3703...... 80 T-7310...... 118 C-2662...... 18 I-1711...... 54 P-4313...... 82 T-7802...... 110 C-2799...... 17 I-4122...... 57 P-4462...... 94 T-7887...... 115 C-3022...... 18 I-5022...... 58 P-4833...... 86 T-8040...... 111 C-3987...... 16 I-5432...... 56 P-6040...... 91 T-8123...... 117 C-4300...... 19 I-5508...... 54 P-6420...... 92 T-8448...... 116 C-6000...... 25 I-5577...... 53 P-6522...... 85 T-9104...... 112 C-6556...... 20 I-5700...... 57 P-6666...... 93 T-9142...... 118 C-7900...... 23 I-5900...... 55 P-6706...... 81 U-6770...... 119 C-8460...... 24 I-6800...... 57 P-7022...... 92 V-2800...... 120 C-8700...... 24 I-8560...... 55 P-7050...... 89 V-4050...... 123 D-1000...... 29 I-9000...... 56 P-7177...... 84 V-7300...... 121 D-2744...... 29 J-4567...... 59 P-7501...... 94 V-8303...... 120 D-2946...... 26 K-2151...... 59 P-7600...... 91 V-8400...... 122 D-3197...... 30 K-3351...... 60 P-7858...... 89 V-8477...... 124 D-3307...... 27 K-4651...... 60 P-8499...... 83 V-9366...... 124 D-3440...... 28 K-5050...... 62 P-8880...... 87 V-9402...... 119 D-3456...... 31 K-6751...... 61 P-9050...... 90 W-2990...... 125 D-3608...... 31 K-7551...... 61 P-9088...... 89 Y-5301...... 126 D-3699...... 32 K-9090...... 61 P-9099...... 88 Y-5399...... 125 D-3899...... 27 K-9609...... 60 P-9600...... 80 Z-1066...... 128 D-4000...... 33 L-4804...... 63 P-9688...... 83 Z-9040...... 128 D-4011...... 28 L-4899...... 62 Q-4747...... 95 Z-9900...... 127 D-4099...... 32 L-5814...... 65 R-1234...... 99 Z-9999...... 127 D-7878...... 26 L-6100...... 63 R-2020...... 98 E-3866...... 34 L-6307...... 64 R-5000...... 96 E-4007...... 38 L-7962...... 66 R-6600...... 100 E-4040...... 40 L-7988...... 66 R-6688...... 101 LC Laboratories® 165 NEW BOSTON STREET WOBURN MA 01801 USA

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34 We Accept VISA MASTERCARD AMERICAN EXPRESS DISCOVER JCB Our 34th Year 1980 – 2014

Reagents for Signal Transduction Research, Therapeutic Discovery and Preclinical Oncology

August 2014 Catalog

Global One-Pricing: Order directly from almost any country! Telephone: (800) 937-3720 Outside the U.S.: 781-937-0777 Fax: (781) 938-5420 www.LCLabs.com