0[T0[T Inhibitors Selleck provides high purity small molecule inhibitors on signaling pathways such as Apoptosis, Akt, MAPK, angiogenesis etc.

Antibodies

Selleck offers a broad selection of monoclonal and polyclonal antibodies to human proteins for various applications, including Western blot, immunohistochemistry, immunofluores- cence, flow cytometry and more. siRNAs

Selleck pre-defined or custom siRNA libraries in human and mouse are available in any of our three market-leading siRNA technologies for screens with efficient, specific and guaranteed knockdown. Screening Libraries

Selleck compound libraries contain over 1000 unique and diverse bioactive compounds suitable for high-throughput screening, cell based high-content screening and chemical biology applications. APIs

Selleck provides about 400 kinds of fine Active Pharmaceutical Ingredients (APIs) and 120 kinds of natural products for global customers. Proteins/Peptides

Selleck produces over 300 grow factors, enzymes, cytokines and chemokines. We also specialize in both peptide synthesis and peptide modifications. Welcome to

What’s in it for me? Selleck is one of the world leading suppliers of high-performance life-science products. We have over 8,000 products which consist of inhibitors, antibodies, RNAis, proteins and peptides those which focus on signaling pathways such as MAPK, PI3K/Akt, and apoptosis. Furthermore, compound libraries for high- throughput screening and high-content screening are also available. Quality Selleck pays great attention to the purity, stability and activity of the products. Not only could Selleck provides the chemical test data, such as HNMR, LC-MS and HPLC, but also provides the reviews overall evaluations of the products from the customers who have used our products. Western Blot, MTT, RT-PCR, ICH photos and figures provide double guarantee for the biological activities of our products in life-science research. If our products have any quality prob- lems, we will unconditionally refund or replace the products . Support Selleck has been leading the way in biology, medical and pharmaceutical science researches, and its reagents and services have been helping scientists world- wide to make successful discoveries. Our team is dedicated to customer satis- faction and our technical experts provide professional support to ensure the best results. Worldwide Relation Selleck has established long-term and stable relationships with more than 10,000 customers from pharmaceutical and biotech companies, universities and research institutions. Selleck has headquarters in United States,Asia and Europe, and also has 38 distributors worldwide. We provide overnight delivery in North America and Europe. Our goal

Our goal is to provide scientists worldwide an easy access to the most innovative life science reagents, and to help them make more significant discoveries. Ordering Information

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Selleck products are applied only for laboratory research and analytical use, and not for any human or veterinary use. They should be used only by technically-qualified individuals or under their direct supervision.

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1. Selleck has 365-day Free Return policy. If you are not satisfied with your purchase, either for protocol-related problems or for product-related problems, you may return items at anytime for free within 365 days from the purchase date. 2. All requests for returns must have prior authorization and must be shipped back to Selleck in the original packaging, and the items are in the same condition. 3. Please have on hand the invoice number, purchase order number or air bil number. 4. Once your return is received and inspected by the QC center (usually within 72 hours of receipt), your refund will be processed and a credit will be automatically applied to your credit card or original method of payment within 7 days. Table of Contents

Angiogenesis/Tyrosine Kinase Pathway 1 EGFR 3 VEGFR/PDGFR 6 FGFR 11 Src-Bcl-Abl 11 IGF-IR 13 HER2 13 c-Kit 14 c-Met 14 FLT-3 15 ALK 16 Vascular Disrupting Agent 16 ETA receptor 16 HIF 16 Syk 17 Tie2 17

Cell Cycle/Checkpoint Pathway 18

ROCK 20 PLK 20 CDK 20 Topoisomerase 22 Microtubule 22 Antimetabolites 24 Telomerase 25 DNA/RNA 25 Checkpoint 26 Dihydrofolate reductase 26

HDAC Signaling 27 HDAC 27 Sir2-like family deacetylase 31

Apoptosis 32 Bcl-2 34 TNF-alpha 35 p53 35 Survivin 35

PARP 36 PARP 38

Aurora Kinase 40 Aurora Kinase 42 Ksp 44

MAPK Signaling 45

MEK 47 p38 MAPK 48 B-Raf 50 JNK 50 PI3K/Akt Signaling 51

PI3K 53 mTOR 56 DNA-PK 57 GSK-3 57 PDK-1 57 ATM 58 Akt 58 Hormone 59

Androgen Receptor 60 Estrogen receptor 60 Aromatase 61 5-alpha-reductase 62 GPR 62

Integrase/CCR5 Pathway 63

CCR5 65 Integrase 65

Proteases/HSP90/HSP70 Pathway 66 Proteasome 68 HSP-70 68 DPP-4 69 HSP-90 69 Aminopeptidase 70 HCV protease 70

Wnt/Hedgehog/Notch Pathway 71 Hedgehog 72 Wnt 72 72

Jak/Stat Pathway 73 Stat 74 Jak 74

Ca/cAMP/Lipid Signaling 75 PKC 76

Neuro Signaling Pathway 77 CGRP 78 COX 78

79 80 GPCR Pathway 81

Vasopressin receptor 82 Angiotensin receptor 82 CB1 receptor 82 83 Serotonin receptor 83 Smooth hened 83 mGluR2/mGlu3 83

Ion Channel 84

CFTR 85 Calcium channel 85 Proton pump 86 Cytochrome P450 87

14a-demethylase 88

Others 90

Factor Xa 91 S1P Receptor 91 sPLA2 91 P-glycoprotein 91 Reverse transcriptase 92 Xanthine oxidase 93 Serotonin reuptake 93 Phosphodiesterase 94 Acetylcholinesterase 95 Adrenergic receptor 96 Histamine 97 GABA 98

Peptide Inhibitors 99 CDK 100 Bcl-2 100 p38 MAPK 100 JNK 100 Oxytocin receptor 100 Glycoprotein receptor 101 Vasopressin receptor 101 LHRHR/GnRHR 101 PTHR 102 Melanocortin-1 receptor 103 PKC 103 SNAPR 103 NKR 103 BDKR/KOR 103 TRH receptor 104 CRF receptor 104 GRF-R 104 Ghrelin receptor 104 Tachykinin NK1 receptor 105 Angiotensin receptor 105 Secretin receptor 105 SSTR 105 GCGR 105 GHSR 106

Angiogenesis/Tyrosine Kinase

Tumor growth is dependent on the perpetual recruitment of host blood vessels to the tumor site. This recruitment process (mainly via angiogenesis) is thought to be triggered by the very same set of genetic alterations as those responsible for other aspects of malignant transformation. Potent oncogenes are able to deregulate expression of both angiogenesis stimulators and inhibitors in cancer cells. For example, mutant ras expression is associated with increased production of VEGF and downregulation of TSP-1. Upregulation of VEGF and angiogenesis can also be induced by constitutive activation of other oncogenic proteins (e.g., EGFR, Raf, MEK, PI3K) acting at various levels on the Ras signaling pathway. The mode and the magnitude of such pro-angiogenic influences can be significantly modified by cell type (fibroblastic or epithelial origin), epigenetic factors (hypoxia, changes in cell density), and/or presence of additional genetic lesions.

Activated oncogenes (e.g. ras, src, HER-2) induce co-expression of angiogenic prop- erties concomitantly with several highly selectable traits (increased mitogen- esis, resistance to apoptosis). On the other hand oncogene-induced reduction in growth requirements may also endow tumor cells with a diminished dependence on proximity to blood vessels. Angiogenesis can be simultaneously suppressed by effective use of the specific oncogene antagonists and signal transduction inhibitors.

Oncogenes and Angiogenesis: Signaling Three-Dimensional Tumor Growth. Janusz Rak, Joanne L Yu et al. J Investig Dermatol Symp Proc. 2000(5):24–33.

 Papers Using Selleck Products

S1010 BIBF1120(Vargatef) Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia MW Harr, PF Caimi, KS et al. Cell Death & Differentiation. 2010(17):1381-1391.

S1012 BMS-536924 PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival Irie HY, Shrestha Y et al. PLoS ONE. 2010;5(7): e11729.

S1014 Bosutinib(SKI-606) Inhibition of ser/thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors Krapf D, Arcelay E et al. J. Biol. Chem. 2010(285): 7977-7985.

S1019 CI-1033(Canertinib) The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin Wonseon Choi, Rainer Wolber et al. J Cell Sci. 2010(123): 3102-3111.

S1021 Dasatinib Anti-leukemic activity of Dasatinib in both p53wild-type and p53 mutated B malignant cells Raffaella Bosco, Marco Rabusin et al. Invest New Drugs 2010.

S1021 Dasatinib/ S1026 Imatinib Mesylate Molecular Characterization of c-Abl/c-Src Kinase Inhibitors Targeted against Murine Tumour Progenitor Cells that Express Stem Cell Markers Raffaella Bosco, Marco Rabusin et al. Invest New Drugs 2010.

S1023 Erlotinib Hydrochloride Dual specificity phosphatase 6(DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK-signaling in lung cancer cells Zhenfeng Zhang, Susumu Kobayashi et al. Carcinogenesis 2010;31(4): 577-586

Mechanisms of myogenic tone of coronary arteriole: Role of down stream signaling of the EGFR tyrosine kinase Ali H. Amin, Zakaria Y et al. Microvascular Research 2011;81(1):135-142

 +-,8 Angiogenesis/Tyrosine Kinase

EGFR (Epidermal growth factor receptor)

S1486 AEE788 Synonyms: NVP-AEE 788 Size Price

H N N AEE788 is a novel dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases (IC50s: EGFR=2 nM, ErbB2=6 5mg N N nM, KDR=77 nM, and Flt-1=59 nM). AEE788 demonstrated antiproliferative activity against EGFR and 10mg NH N ErbB2-overexpressing cell lines and inhibited the proliferation of human umbilical vein endothelial cells. Oral administration of AEE788 to mice resulted in high and persistent compound levels in tumor tissue. 50mg

S1011 BIBW2992 Synonyms: Tovok Size Price

F BIBW2992 shows potent activity against EGFR and HER2. BIBW2992 was effective in inhibiting survival of 5mg H1666 or NCI-H1975 EGFR, with IC50s belowbelow 100 nM . Assessed in a standard xenograft model of the 10mg Cl NH H epidermoidepidermoid carcinoma cell line A431.DailyA431.Daily oraloral treatmenttre with BIBW2992 at 20 mg/kg for 25 days resulted in N 25mg N N dramaticdramatic tumor regression with a cumulative treatreated/controlt tumor volume ratio (T/C ratio) of 2%. O N O Feed P-EGFR S1011 BIBW2992

Western blot analysis of extracts from EGF, EGFR O BIBW2992 treated T47D breast denocarcinoma cell line using antibodies as indicated. 0nM 0.01nM 0.1nM 1nM 0nM BIBW2992 Produced Independently by our customer Dr.Zhang, Tianjin Medical University + + + + - EGF(100ng/ml)

S1028 Lapatinib Ditosylate Synonyms: Tykerb, Tyverb, GW-572016 Size Price

Lapatinib have IC50 values against purified EGFR and HER2 of 10.2 and 9.8 nM, respectively. And IC50 25mg N >10000nM against c-Raf-1, MEK, ERK, CDK1, CDK2, p38 and VEGFR-2.The IC50s for inhibition of cell 50mg O N !"#"$#)'*;

O OH O 0.5μM 0.05μM Growing S OH Lapatinib 0μM 0μM 5μM Feed S EGF (100ng/ml) - + +++ - S1028 Lapatinib 100 O O p-ErbB2 (Tyr.1221/1222) lapatinib lapatinib+7839

p-Tyrosine SKBR3 cells were starved for 4h in Sheddase inhibition

p-Akt (Ser.473) serum-free medium and treated as improves the ability of 50

Total Akt indicated; or left growing in complete lapatinib to inhibit BT-474

medium (last lane). cell growth. % controlcellgrowth p-Erk1/2 (Thr.202/Tyr.204) 0 Total Erk1/2 1 10 100 1000 10000 Provided from our customer Carl Uli Bialucha,Cold Spring Harbor Lapatinib conc (nM) beta-Actin Laboratory ,NY,USA

S1025 Gefitinib Synonyms: ZD-1839, Iressa Size Price

O N The monolayer growth of these EGF-driven untransformed cells such as MCF10A is inhibited by ZD1839 with 25mg an IC50 of 20 nM, similar to its IC50 in vitro for EGFR and consistent with effective inhibition of EGFR in vivo. N 50mg N O Cell line characteristics and sensitivity to Gefitinib at 1uM are 59% inhibition for MDA-MB-231, 74% inhibition O HN Cl for A431, 81% inhibition for SKBr3,60% inhibition for SKOV3, 33% inhibition for BT474,52% inhibition for 100mg MCF-7, 28% inhibition for T47D, respectively. F

Feed S1025 Gefitinib Effects of shRNA-mediated RECK depletion on EGFR signaling in MEFs. MTT assay result. 0-500nM (a) Immunoblotting (IB) of the indicated proteins in wild-type MEFs Gefitinib (Selleck S1025) transduced with the indicated shRNAs and cultured for 48 h in the presence treated with H1299, H358, of 0.1% dimethyl sulfoxide(DMSO; vehicle) or 1 mM gefitinib H25 and HCC827 cell lines (S1025, Selleck Chemicals,Houston, TX, USA). by 72h, Proliferation rate (b) Immunoprecipitation from whole lysates of cells from panel a with was tested. an anti-phosphorylated tyrosine (pTyr) antibody. Precipitates from 500 mg protein in whole cell lysates (upper) or 20 mg protein in whole cell lysates Data provided by our customer (lower) were analyzed by IB with anti-EGFR antibody. Vicky Tin，The University of Data from Oncogene (2010), 1–14 using our product. Hong Kong. S1392 Pelitinib Synonyms: EKB-569, WAY-EKB 569 Size Price

Pelitinib is a 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity. Pelitinib 5mg O N O irreversibly binds covalently to EGFR, ErbB-1, -2 and -4, thereby inhibiting receptor phosphorylation and signal N 25mg N CN transduction and resulting in apoptosis and suppression of proliferation in tumor cells that overexpress these H HN receptors. Pelitinib inhibits EGF-induced phosphorylation of EGF-R and the growth of tumors that overexpress 50mg

F EGF-R in animal models. Cl

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase +-,8

S1194 CUDC-101 Size Price

CUDC-101 has novel structure incorporating HDAC (IC50 4.4 nM) inhibitory functionality into the 5mg pharmacophore of the EGFR C50 2.4 nM) and HER2 (IC50 15.7 nM) inhibitors. CUDC-101 exhibits efficient HN 10mg H antiproliferative activity with greater potency than vorinostat (SAHA), erlotinib, lapatinib. CUDC-101 inhibition N O HO N in various cancer xenograft models including NSCLC, liver, breast, head and neck, colon, and pancreatic 25mg O cancers. O N Feed S1194 CUDC-101 Effect of CUDC101 on the viability was Breast Cancer Cell line MDA-MB-231 detected by WST-1 method after 3 days Breast cancer cells were starved for 16 hrs, treatment in endometrial cancer cell Acetyl-H 3 100ng/ml EGF for 15 min with the indicated line Hec50 and Ishikawa and ovarian concentrations cancer cell line SKOV3, Caov3 and PA1. H3 Produced Independently by our customer Data from our customer Dr Meng Xiangbing, CUDC101(M) 0 0.01 0. 1 1.0 10.0 20.0 Dr.Zhang, Tianjin Medical University The University of Iowa.

S1023 Erlotinib HCl Synonyms: Tarceva, CP-358774, OSI-774, NSC 718781 Size Price

O N 50mg O Erlotinib Hydrochloride inhibit activity against isolated tyrosine kinase(IC50, 2 nmol/L), to reduce HER1/EGFR O N autophosphorylation in intact human tumor cells in vitro (IC50, 20 nmol/L), and to inhibit the EGF-dependent O 100mg HN proliferation of cells. It acts by inducing the expression of the cell-cycle inhibitor p27, and suppressing the HCl expression of the cell-cycle promoter cyclin D1, thereby blocking cell-cycle progression at the G1 phase. 500mg

PC9 cell DUSP6 is regulated by EGFR/ERK inhibition in NSCLC cell lines. HCC827 cell 3h 6h 9h 3h 6h 9h Feed Time(hr) 0 Time(hr) 0 S1023 Erlotinib Hydrochloride DTUDTU DTU EDErEDErEDEr Protein expression levels were assayed by immunoblot for P-EGFRV P-ERK Downregulation of DUSP6 is directly dependent on inhibition of P-ERK/ETS1 phosphor-EGFR at indicated tyrosine sites, total-EGFR, Y-1068 T-EGFR T-ERK signaling and only indirectly on inhibition of EGFR activity as demonstrated phosphor-ERK, total-ERK, ETS1, DUSP6 and GAPDH demonstrating P-ERK T-ERK by DUSP6 expression in PC9 cells correlating closely with p-ERK activity. suppression of DUSP6 following inhibition of activated ERK (P-ERK) DUISP6 ETS1 and ETS1 levels in the presence of appropriate drug for each of the DUSP6 GAPDH Data form Carcinogenesis Advance Access Published online on Jan. 2010 following cell lines: HCC827 cells treated with erlotinib GAPDH using our inhibitor

S1143 AG-490 Synonyms: Tyrphostin AG490 Size Price

O AG490 is a member of the tyrphostin family of tyrosine kinase inhibitors. The most-studied targets of AG490 25mg HO are the Janus kinases (JAKs: JAK-2, JAK3/STAT, JAK3/AP-1, and JAK3/MAPK), a family of tyrosine kinases N 100mg H that phosphorylate and thus activate the STAT transcription factors. AG490 inhibits the proliferation of several 200mg HO cell types including leukemia cells and fibroblasts. AG490 is also selective inhibitor of EGFR tyrosine kinase N |}~]"€?$])'*‚^ƒ$

S2192 AZD8931 Size Price

1(: AZD8931 is a novel potent reversible small molecule epidermal growth factor receptor, ErbB2 (HER2) and 10mg HN Cl ErbB3 inhibitor with an IC50 of 4, 3, 4 nM, respectively. It has a unique pharmacologic profile providing O F 50mg O N equipotent inhibition of EGFR, ErbB2, and ErbB3 signaling and showing greater antitumor activity than agents N with a narrower spectrum of erbB receptor inhibition in specific preclinical models. 200mg N O N H

S2150 Neratinib Synonyms: HKI-272 Size Price

O N Neratinib is an orally available, irreversible tyrosine kinase inhibitor with IC50 of 59 nM and 92 nM for HER2 5mg

HN and EGFR, respectively. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing N 25mg N HN Cl O autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the

O receptor. Neratinib also inhibits the EGFR kinase and the proliferation of EGFR-dependent cells. 100mg N S1079 PD153035 HCl Synonyms:Synonyms: ZM 252868, 252868, AG 1517, AG 1517,Tyrphostin Tyrphostin AG 1517, SU AG 5271, 1517 PD 153035 Size Price

PD153035 effectively blocks the enhancement of mitogenesis, induction of early gene expression, and 10mg oncogenic transformation that occur in response to EGFR stimulation. With human fibroblasts and epidermoid HCl 50mg HN Br carcinoma cells, PD153035 at nanomolar concentrations rapidly inhibits EGFR autophosphorylation. With O breast and ovarian cancer cells, PD153035 not only blocks cell growth via inhibition of EGFR, but also 200mg N upregulates the expression of the tumor suppressor retinoic acid receptor-beta 2. O N Feed S1079 PD153035 Hydrochloride

PD153035 Vandetanib Gefitinib Inhibition of orthopoxvirus replication and spreading correlates with blocking of ‚„ ]?"?Z†[$!* lysates obtained from VACVplaque reduction tests for analysis of EGFR-ERK1/2 signaling and VACV proteins. As an indicative band for VACV a 30KD a protein was depicted from detection of total VACV proteins by apolyclonal antibody in cell lysates of infected Hep2 cells. Data from our customer Dr.Saraswati Sukumar, Johns Hopkins University School of Medicine.

 Solutions to Signal Transduction Research +-,8 Angiogenesis/Tyrosine Kinase

S1046 Vandetanib Synonyms: Zactima, ZD6474 Size Price

Vandetanib is a potent inhibitor of KDR tyrosine kinase activity (IC50= 40nM) and a submicromolar inhibitor of 50mg N EGFR tyrosine kinase (IC50= 500nM). The activity of Vandetanib versus KDR tyrosine kinase translates into O N 200mg potent inhibition of VEGF-stimulated endothelial cell proliferation in vitro (IC50 =60 nM). Vandetanib blocks the N enzymatic activity of RET-derived oncoproteins at a one-half maximal inhibitory concentration of 100 nM. 500mg O HN Feed S1046 Vandetanib

F Br Inhibition of orthopoxvirus replication and spreading correlates with blocking of EGFR signaling by PD15303, Vandetanib and [$ Western blot of cell lysates obtained from VACV plaque reduction tests for analysis of EGFR-ERK1/2 signaling and VACV proteins. As an indicative band for VACV a 30KDa protein was depicted from detection of total VACV proteins by a polyclonal antibody in cell lysates of infected Hep2 cells. Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine.

S1056 BMS-599626 Synonyms: AC480 Size Price

O HCl BMS-599626 inhibited HER1 and HER2 with IC50 of 20 and 30 nmol/L, respectively, and was highly selective 5mg H when tested against a broad panel of diverse protein kinases.BMS-599626 abrogated HER1and HER2 O N HN N 25mg N signaling and inhibited the proliferation of tumor cell lines that are dependent on these receptors, with IC50 in H N O N N F *"$<)'$ 100mg N Feed S1056 BMS-599626

breast cancer cells were starved for 16 hrs, 100ng/ml EGF for 15 min with the indicated concentrations.

Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1170 WZ3146 Size Price

O WZ3146 is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype 10mg N O N H EGFR, than quinazoline-based EGFR inhibitors (HKI-272 and CL-387,785) in vitro. WZ3146 has a 300-fold N Cl 50mg N lower half-maximum inhibitory concentration (IC50<10nM) against the PC9GR (delE746_A750/T790M, 200mg N N gefitinib-resistant) cells compared with clinical-stage inhibitors such as HKI-272. H S1173 WZ4002 Size Price

O WZ4002 is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype 10mg N O N H EGFR, than quinazoline-based EGFR inhibitors (HKI-272 and CL-387,785) in vitro. WZ4002 treatment N Cl 50mg N resulted in significant tumour regressions compared with vehicle alone in both T790M-containing murine N N 100mg H models. O S1179 WZ8040 Size Price

O WZ8040 is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype 10mg N s N H N Cl EGFR, than quinazoline-based EGFR inhibitors (HKI-272 and CL-387,785) in vitro. WZ8040 has a 300-fold N 50mg lower half-maximum inhibitory concentration (IC50<10nM) against the PC9GR (delE746_A750/T790M, N N H gefitinib-resistant) cells compared with clinical-stage inhibitors such as HKI-272. 200mg

S2406 Chrysophanic acid Synonyms: NSC 37132, NSC 646567 Size Price

1(: O Chrysophanic acid is an EGFR/mTOR pathway inhibitor. Chrysophanic acid preferentially blocked proliferation 10mg in SNU-C5 cells but not in other cell lines with low levels of EGFR expression. Chrysophanic acid inhibited 25mg EGF-induced phosphorylation of EGFR and suppressed activation of downstream signaling molecules, such as AKT, ERKmTOR/p70S6K. Chrysophanic acid (80 and 120 μM) significantly blocked cell proliferation when 100mg combined with the mTOR inhibitor, rapamycin. OH O OH

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase +-,8<+-,86*-,8

S2216 Mubritinib Synonyms: TAK 165,TAK165 Size Price

N N 1(: N Roscovitine is a potent EGFR and p34cdc2 inhibitor with IC50 of 6 nM and 0.2 μM, respectively. Roscovitine 10mg displays > 4000-fold selectivity over EGFR, FGFR, PDGFR, JAK1 and Src. Roscovitine exhibits potent 25mg O antiproliferative effects in ErbB2-overexpressing cancer cell lines and significantly inhibits bladder, breast and N O prostate cancer xenograft growth in vivo. 50mg F F F S2205 OSI-420 Synonyms: Desmethyl Erlotinib,CP-473420 Size Price

O N 1(: O OSI 420 is an active metabolite of erlotinib which is an orally active EGFR tyrosin kinase inhibitor with IC50 of 10mg HO N O 2 and 20 nM for the inhibition of human EGFR and EGFR autophosphorylation in tumor cells. OSI-420 NH 50mg HCl exposure (AUC) in plasma was 30%of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. 200mg

VEGFR / PDGFR

Synonyms: Linifanib, AL-39324, RG3635 S1003 ABT-869 Size Price

H H ABT-869 is a KDR inhibitor (IC50=4nM) but has much less activity (IC50s>1mM) against unrelated RTKs, 10mg NH2 N N N soluble tyrosine kinases, or serine/threonine kinases. The inhibition of ABT-869 inhibits RTK phosphorylation HN O 50mg F (IC50=2, 4, and 7 nM for PDGFR-B, KDR, and CSF-1R, respectively) and VEGF-stimulated proliferation (IC50 = 0.2 nM for human endothelial cells) in cellular assays. 100mg

R:Radiation 16 Gy Feed S1003 ABT-869

nM nM+R uM uM ABT-869 0 10nM 100 0 1uM 2.5uM 0uM+R 10 1uM+R 2.5uM+R Western blot analysis of extracts Bcl-xl, Bcl-2; 0-2500 nM ABT-869 Bcl-xl was added; Cell cutured with 16Gy radiation or not. Data produced independently by our customer Dr.Zhang,Tianjin Medical University Bcl2

S1064 Masitinib Synonyms:Synonyms: HKI-272 AB1010, Masivet Size Price

N Masitinib is Phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. In Ba/F3 cells expressing 25mg human wildtype KIT, masitinib dose-dependently inhibited SCF-induced cell proliferation with an IC50 of 150 N O 50mg S N N N nM. H H N 100mg

S1490 AP24534 Synonyms:Synonyms: ZM Ponatinib 252868, AG 1517, Tyrphostin AG 1517 Size Price

N AP24534 (Ponatinib), a potent, orally available multitargeted kinase inhibitor, which is active against 25mg N N pan-BCR-ABL native (IC50: 0.37nM) and mutated form (IC50: 0.3-2.0nM), VEGFR2 (IC50: 1.5nM), FGFR1 50mg N |}~]"Š $'ƒZ „ ‚ |}~]"Š $'ƒ Œ\ |}~]"Š"$<'ƒ$ ;„<]?< ^~‚;^Œ H N N mutants with low nM IC50s in cellular assays, suppressed BCR-ABL driven tumor growth in mice, and 200mg O CF3 completely abrogated resistance in cell-based mutagenesis screens. S1207 AV-951 Synonyms: Tivozanib Size Price

N AV-951, a novel oral quinoline urea derivative, is an orally bioavailable inhibitor of VEGFRs 1, 2 and 3 with 10mg Cl O O N potential antiangiogenic and antineoplastic activities. AV-951 blocks the proliferation and migration of 50mg O NH endothelial cells in vitro, and suppresses angiogenesis and growth of human tumor xenografts in vivo. The O NH compound is for the treatment of renal cell carcinoma and non-small cell lung carcinoma, and other 100mg O gastrointestinal cancer patients.

S1084 Brivanib Synonyms: BMS-540215 Size Price

H N Brivanib is hydrolyzed to the active moiety BMS-540215 in vivo. BMS-540215 is an ATP-competitive inhibitor 10mg of human VEGFR -2, with an IC50 of 25 nmol/L and Ki of 26 nmol/L. In addition, it inhibits VEGFR-1 (IC50 = O 50mg F 380 nmol/L) and VEGFR-3 (IC50 = 10 nmol/L). BMS-540215 also showed good selectivity for FGFR-1 (IC50 N O OH 100mg N = 148 nmol/L), FGFR-2 (IC50 =125 nmol/L), and FGFR-3 (IC50 = 68 nmol/L). N

 Solutions to Signal Transduction Research <+-,86*-,8 Angiogenesis/Tyrosine Kinase

S1017 Cediranib Synonyms: AZD2171, Recentin Size Price H N AZD2171 is a highly potent inhibitor of recombinant KDR tyrosine kinase activity in vitro (IC50 < 1 nmol/L). 10mg O Additional activity is observed against the kinase associated with Flt-1 (IC50= 5 nmol/L) and the VEGF-C and O F 25mg N VEGF-D receptor Flt-4 (IC50 <3nmol/L). The inhibitory activity of AZD2171 was also examined against each 50mg N O N recombinant PDGFR-related kinase in vitro because of their structural similarity to the VEGF family of receptors. S1018 CHIR-258 Synonyms: TKI-258, Dovitinib Size Price

CHIR-258 potently inhibits FGFR3 with an IC50 of 5 nM in vitro kinase assays and selectively inhibited the 10mg O N N N growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3. 50mg N HN Feed H IP:FGFR3 S1018 CHIR-258 200mg IB:Phos-tyr NH2 The effect of PD173074 on FGFR3 phosphorylation and proliferation of IB:FGFR3 FGFR3-expressing bladder tumour cell lines. RT112 cells were exposed to PD173074 (PD) F PD173074 0h 2h 6h 24h TK SU (500 nM) for 0–24 h, TKI-258 (TK) (500 nM) or SU5402 (SU) (5 mM) for 1 h. Cells were lysed, FGFR3 was immunoprecipitated (immunoprecipitated, IP) and blots (immunoblot, IB) pERK were probed for phospho-tyrosine and reprobed for FGFR3 or (C) probed for phospho-ERK Total ERK and reprobed for total ERK.t Con TK PD SU Data from British Journal of Cancer (2010) using our product.

S2202 NVP-BHG712 Synonyms:Synonyms: HKI-272 CP673451 Size Price

O NVP-BHG712 is a small molecule specific EphB4, VEGFR2, c-raf, c-src and c-Abl kinase inhibitor with ED50 10mg * ] 'Z <$Z "$

CYC116 is an orally bioavailable,small molecule Aurora kinase/VEGFR2 inhibitor with antineoplastic activity. 10mg N CYC116 inhibits Aurora kinases A and B and VEGFR2, resulting in disruption of the cell cycle, rapid cell death, H 50mg N N NH2 and the inhibition of angiogenesis. CYC116 has a unique target profile involving both cell cycle and S angiogenesis inhibition mechanisms. In preclinical studies, it has antitumor activity in both solid tumors and 200mg N N hematological cancers.

O Feed Histone H3 S1171 CYC116

p-Histone H3 Western blot analysis of Histone-H3, p-Histone-H3, Aurora A, ;€;^~“"")'~~#$ Aurora A

p-Aurora Produced independently by our customer Dr.Zhang,Tianjin Medical University. A/B/C 0μM 0.001μM 0.01μM 0.1μM 1μM 10μM CYC116

S1164 E7080 Size Price

O NH2 E7080 is the most potent dual inhibitor of VEGF-R3 tyrosine kinase (IC50=5.2 nM) as well as VEGF-R2 10mg O tyrosine kinase (IC50=4.0 nM) among those small-molecule inhibitors of VEGF-R kinases, such as sunitinib, 50mg O sorafenib, and CEP-7055. IE7080 suppresses lymph node and lung metastases of human mammary breast HN N tumor MDA-MB-231 via inhibition of angiogenesis and lymphangiogenesis in vitro. It has been used in phase 100mg N O H I clinical trial against hepatocellular carcinoma and non-small cell lung carcinoma. Cl S1026 Imatinib MesylateSynonyms: Gleevec, Glivec, CGP-57148B, STI-571 Size Price

N Imatinib Mesylate is a reversible tyrosine kinase inhibitor effective in treatment of CML, gastrointestinal stromal 10mg N H H tumors, eosinophilic disorders, and systemic mast cell disease. The drug binds preferentially to ATP–binding N N N N 200mg *€Z„ ‚Z;^Œ$}~]"€* ~„[;?$_) O N O '$_)'Z$;<$<)'Z€*\^€]‘$’ 500mg HO S ?‘$<’$#)'$ O Feed S1026 Imatinib Mesylate

Cell Viability assay results. A2C12, BetaD5, GammaA3, GammaD12, A549, CaCo2, HepG2 cell lines were treated with imatinib for 96h and 24h.

Data from our customer Dr Thomas Krüwel, Fraunhofer-Institute for Toxicology and Experimental Medicine

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase <+-,86*-,8

S1363 Ki8751 Size Price F F H H N N Ki8751 is a VEGFR-2 inhibitor. It inhibited VEGFR-2 phosphorylation at an IC50 value of 0.90 nM, and also 5mg O „ ‚*€„ ‚#'<"'Z$} O F 10mg O have any inhibitory activity against other kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. Ki8751 suppressed the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC) on 25mg N O a nanomolar level. S1557 KRN 633 Size Price

Cl H H N N KRN 633 is a cell-permeable, reversible, ATP-competitive VEGFR kinase inhibitor with IC50 of 170 nM, 160 10mg 'Z]'*†‚Z†‚Z†‚?Z$}„ ‚ O 50mg O concentrations only (IC50 = 0.97 μM and 4.33 μM, respectively). Although not cytotoxic to cancer cells, O N KRN633 exhibits excellent in vivo antitumor activity due to its inhibitory effects on vessel formation and 200mg O N vascular permeability. S1361 MGCD-265 Size Price

H H N N MGCD265 is a tyrosine kinase inhibitor that targets the c-Met, VEGFR-1, VEGFR-2, VEGFR-3, RON and TIE2 10mg

S O receptor tyrosine kinases, which appear to play key roles in tumour development and blood vessel formation O 50mg F (angiogenesis) and tumour survival. MGCD265 is currently in phase I single-agent clinical trials for solid N S tumour cancers and in phase II trials for solid tumours and NSCLC. 200mg N N S2161 RAF265 Synonyms: CHIR-265 Size Price

N F O F 10mg N N ‚*#]‚*†‚}~]"**]")'$‚* HN H F N of the Ras/Raf/MEK/ERK signal-transduction pathway, which controls cell proliferation, differentiation, and N 25mg apoptosis in mammalian cells. Raf265 also has anti-angiogenic activity through inhibition of VEGFR. F 50mg F F

S1032 Motesanib Diphosphate Synonyms: AMG-706 Size Price

H H 10mg N N N AMG-706 (Motesanib) selectively targets and inhibits VEGFR1/2/3 (IC50: 2 nM /3 nM /6 nM), PDGFR (84nM), NH O c-kit (8nM), and Ret (59nM) receptors, thereby inhibiting angiogenesis and cellular proliferation. This 50mg compound also performed antitumor activity in breast cancer xenografts and was currently being studied in 100mg 2H3PO4 clinical trials for the treatment of thyroid cancer and other advanced solid tumors. N S1244 MP-470 Synonyms: HKI-272 Size Price

N N MP470 is a multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Met, c-Kit, PDGFR- 10mg O N Z ? }~]" * ] )'$ '„<" \;  50mg N apoptosis. The cytotoxicity of MP470 was evaluated on prostate cancer cell lines (LNCaP, PC-3 and DU-145). NH O S €**Œ\~„„~?}~]"*<)'‘)'Z$ 200mg O S1220 OSI-930 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Size Price

S H F N F OSI-930 is a multi-targeted tyrosine kinase inhibitor that is designed to act as a potent co-inhibitor of the 5mg F O receptor tyrosine kinases c-Kit (IC50: 9.5 nM) and VEGFR-2 (IC50: 10.1 nM). OSI-930 targets both cancer cell O 25mg NH proliferation and angiogenesis in selected tumors. In preclinical studies, OSI-930 shows broad efficacy in tumor models representative of small cell lung cancer, glioblastoma, colorectal, renal, head and neck, 50mg

N non-small cell lung cancer and gastric cancers.

S1035 Pazopanib HCl Synonyms: GW786034, VOTRIENT Size Price

H Pazopanib showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM 25mg N N N N for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine N 100mg N receptor kinases PDGFR beta, c-Kit, FGF-R1, and c-fms with IC50 of 84, 74, 140,and 146 nM, respectively. O „<]"*”")'•Z 500mg S H2N O HCl –*~_|$_)'ƒ$

S1178 BAY 73-4506 Synonyms: Regorafenib Size Price F F F BAY 73-4506 is an orally bioavailable multikinase inhibitor targeting both the tumor and its vasculature. BAY 5mg HN Cl 73-4506 binds to and inhibits VEGFR-2 and -3, and tumor cell signaling kinases (RET, c-Kit, PDGFR, and 10mg HN b-Raf), which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. This drug shows O F potent, oral activity in a wide variety of preclinical xenograft models. 25mg

N O

HN O

 Solutions to Signal Transduction Research <+-,86*-,8 Angiogenesis/Tyrosine Kinase

S1264 PD173074 Size Price

O PD173074 is a potent, cell-permeable and ATP-competitive inhibitor of FGFR1 (IC50 = 21.5 nM). PD173074 5mg N O inhibits PDGFR and c-Src only at much higher concentration (IC50 = 17,600 nM, 19,800 nM, respectively) and 10mg N N N NH H exhibits little effect against EGFR, InsR, MEK, and cPKC even at concentrations as high as 50,000 nM. O NH 50mg N

Synonyms: Sutent, SU-11248 S1042 Sunitinib Malate Size Price

O Evaluating the ability of SU11248 to inhibit ligand-dependent receptor phosphorylation in cells, the effect of 10mg SU11248 on ligand-dependent proliferation of cells was examined. SU11248 inhibited VEGF- and NH 50mg N FGF-induced proliferation of HUVECs with IC50 values of 0.04 and 0.7 μM, respectively. SU11248 also inhibited PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRa or PDGFRb with IC50 values 200mg F N H of 0.03 and 0.07 μM, respectively. O O N H HO OH Feed S1042 Sunitinib Malate O OH Experimental layout for VEGF signaling blocking and LCMV infection in WT mice. Mice received two injections on day 0 and 3 p.i. of Abs as described in Material and Methods, or daily gavage of the VEGFR/PDGFR-inhibitor sunitinib. Data published in February 25,2010;Dol 10.1182/blood-2009-10-250118,provided by

our customers Varsha Kumar, Theodor Kocher Institute,University of Bern,Switzerland

S2201 BMS 794833 Synonyms: BMS794833 Size Price

F 1(: BMS-794833, a potent ATP competitive Met/VEGFR-2 kinase inhibitor, demonstrates enhanced activity 10mg versus both Met-dependent and Met-insensitive tumor lines. BMS-794833 also inhibits Ron, Axl and Flt-3 with O 50mg H IC50 values <3 nM. The compound was selective versus a panel of >200 additional RTKs, non-RTKs and F N NH N serine/threonine kinases based on biochemical or Ambit binding assays. In cell culture, BMS-794833 inhibited 200mg O H2N O the proliferation of human tumor cell lines containing constitutively activated Met receptor. Cl

S1040 Sorafenib Tosylate Synonyms: Nexavar, Bay 43-9006 Size Price

CF3 O Cl O O N H Sorafenib Tosylate is a novel, small molecular inhibitor of several tyrosine protein kinases (VEGFR and 10mg N N N PDGFR) and Raf/MEK/ERK cascade inhibitor with an IC50 of 6, 22, 38 nM for Raf-1, wt b-raf and V599E H H 50mg mutant b-raf. It does not significantly inhibit MEK-1 or ERK-1 activity (IC50 >10 μM). It interacts synergistically O S with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for 200mg HO O the Akt and JNK pathways in mediating synergism. S1138 Brivanib alaninate Synonyms: BMS-582664 Size Price H N Brivanib is hydrolyzed to the active moiety BMS-540215 in vivo. BMS-540215 shows potent and selective 10mg O inhibition of VEGFR and FGFR tyrosine kinases. BMS-540215 is an ATP-competitive inhibitor of human (R) F 50mg N VEGFR-2, with an IC50 of 25 nM and Ki of 26 nmol/L. In addition, it inhibits VEGFR-1 (IC50 =380nM) and O O N 200mg O N VEGFR-3 (IC50 = 10 nM). BMS-582664 was prepared in an effort to improve the aqueous solubility and oral (S) bioavailability of the parent compound BMS-540215. NH2 S2475 Imatinib Synonyms: STI571, Gleevec, Glivec Size Price

1(: Imatinib is a number of tyrosine kinase enzymes specific inhibitor. It act by specifically inhibiting a certain 10mg N enzyme that is characteristic of a particular cancer cell, rather than non-specifically inhibiting and killing all N H H 25mg N N N N rapidly dividing cells, and served as a model for other targeted therapy modalities through tyrosine kinase inhibition. As this is now a constitutively active tyrosine kinase, it is used to decrease bcr-abl activity. It is being O N 50mg used as an experimental agent to suppress PDGF.

S1111 Foretinib Synonyms: XL880, GSK1363089, GSK089, EXEL-2880 Size Price

H H F N N GSK1363089 (XL880) is an orally bioavailable,small molecule Met/VEGFR2 inhibitor with potential 10mg O O O F antineoplastic activity. This compound binds to and selectively inhibits HGF receptor c-Met (IC50 of 0.4 nM) 50mg O and VEGFR2, which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. 200mg N O N O S1119 XL184 Size Price

H N HN XL-184 is an orally bioavailable, small molecule RTK inhibitor. Specifically, XL184 appears to have a strong 10mg O F O affinity for the Met and VEGFR2, which may result in inhibition of tumor growth and angiogenesis, and tumor 50mg O regression. This agent has also been shown to inhibit mast/stem cell growth factor (c-Kit), Flt3 and Tie-2.

N O N H NH

N O

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only--- Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase <+-,86*-,8

S1470 TSU-68 Synonyms: HKI-272 SU6668 Size Price O

OH TSU-68, a molecular-targeting drug, has the effect on blocking the tyrosine kinase phosphorylation of the 10mg receptors not only for VEGF but also for PDGF and bFGF, and inhibiting angiogenesis. Studies using in vivo N 50mg H experimental models of cancers such as colon cancer have reported that TSU-68 has the effect on inhibiting O tumor proliferation and metastasis through the inhibition of tumor angiogenesis. In vitro TSU-68 does not 200mg N H influence the proliferation of ovarian cancer cells. S1101 Vatalanib Synonyms:Synonyms: ZM Vatalanib 252868, succinate, AG PTK/ZK, 1517, CGP-79787DTyrphostin AG 1517 Size Price

N O N **Z„‘}~]""$"?)' ‚Z"$")'Z"$€' 100mg Flk,0.66 uM to Flt-4,0.73 uM to c-Kit. Selective inhibition of VEGFRs by PTK787/ZK 222584 leads to inhibition N 200mg O of primary tumor growth and development of metastases in murine renal cell carcinoma. PTK787/ZK 222584 HN caused no obvious side effects in the RENCA model. PTK787/ZK222584, causes significant anti-arthritic 300mg . 2HCl effects in models of rheumatoid arthritis. F Br S1005 Axitinib Synonyms:Synonyms: ZM AG-013736 252868, AG 1517, Tyrphostin AG 1517 Size Price

In transfected or endogenous RTK-expressing cells, axitinib potently blocked growth factor-stimulated N 50mg phosphorylation of VEGFR-2 and VEGFR-3 with average IC50 values of 0.2 and 0.1 to 0.3 nmol/L, 100mg O S respectively. Cellular activity against VEGFR-1 was 1.2 nmol/L, equivalent to an absolute IC50 of -0.1 nmol/L, HN N based on protein binding of axitinib. The potency against Flk-1 in Flk-1-transfected NIH-3T3 cells was 0.18 200mg N H nmol/L, similar to that of its human homologue.

Feed S1005 Axitinib Phospho-VEGFR-2 HUVECs were starved O/N in EBM-2 basal medium with 1% FBS and antibiotic. Cells were pre-treated with Axitinib at 0.1, 1 and 10 nM VEGFR-2 concentrations. VEGF stimulation was 50ng/ml for 10 minutes before cells were collected and protein isolated for immunoprecipitation with Axitinib (nmol/L) 0 0 0.1 1 10 VEGFR2 followed by immunoblotting with VEGFR-2 and phospho-VEGFR-2.

VEGF (50 ng/ml) - + + + + Data from our customer Dr Cheri Pasch, UW.

S1010 BIBF1120 Synonyms: Vargatef Size Price

O The targeted kinases of BIBF1120 include all three VEGFR subtypes (IC50 = 13–34 nmol/L), PDGFRa and 5mg N N N PDGFRh (IC50 = 59 and 65 nmol/L), and FGFR types 1, 2, and 3 (IC50 = 69, 37, and 108 nmol/L, 10mg respectively). BIBF 1120 inhibits MAPK and Akt signaling pathways in three cell types contributing to angiogenesis, endothelial cells, pericytes, and smooth muscle cells, resulting in inhibition of cell proliferation 50mg NH (EC50=10–80 nmol/L) and apoptosis. O Feed S1010 BIBF1120 O N H O PBLs from CLL5 were treated with vehicles (0.1% ethanol and 0.005% DMSO), 10 nM dexamethasone, 50 nM BIBF 1120, or both for 24 h. Cells were also treated with 0.1% ethanol or 10 nM dexamethasone in the presence of either nonphosphorylated (control) EGQYEEIP or hosphorylated

EGQY*EEIP H2O soluble peptides (200 nM) for 24 h. Cell death was measured in triplicate by trypan blue dye exclusion.

Data published in Cell Death and Differentiation, 2010, 1-11 using our product.

S1486 AEE788 Synonyms: NVP-AEE 788 Page 3

S1046 Vandetanib Synonyms:Synonyms: ZM Zactima, 252868, ZD6474 AG 1517, Tyrphostin AG 1517 Page 5

 Solutions to Signal Transduction Research ,-,89XI(IX'HR Angiogenesis/Tyrosine Kinase

FGFR (Fibroblast growth factor receptor)

S1107 PHA-739358 Synonyms:Synonyms: HKI-272 Danusertib Size Price

H CHIR-258(Dovitinib) is a highly potent, novel multitargeted growth factor receptor kinase inhibitor with IC50 of 5mg N N 1, 2, 10, 8, 27, 36 nM for FLT3, c-KIT, VEGFR1/2/3, PDGFRß and CSF-1R, respectively. It potently inhibits O 10mg HN N FGFR3 with an C50 of 5 nM in in vitro kinase assays and selectively inhibited the growth of B9 cells and human myeloma cell lines expressing wild-type or activated mutant FGFR3. Antiproliferative activity of CHIR-258 50mg O O against MV4;11 was ~24-fold greater compared with RS4;11.

N P-Aurora A/B/C Feed S1107 PHA-739358 N Aurora B Western blot analysis of Histone-H3, p-Histone-H3, Aurora A, Aurora B,

Aurora A ;€;^~“"$""")'„[;?_?]‘$ Produced independently by our customer Dr.Zhang,Tianjin Medical University. Histone H3

P-Histone H3 10 1 0.1 0.01 0.001 Control )'

S1018 CHIR-258 Synonyms: HKI-272 TKI-258, Dovitinib, CHIR258, TKI258 Page 7

S1490 AP24534 Synonyms:Synonyms: ZM Ponatinib 252868, AG 1517, Tyrphostin AG 1517 Page 6

S1010 BIBF1120 Synonyms:Synonyms: ZM Vargatef 252868, AG 1517, Tyrphostin AG 1517 Page 10

S1264 PD173074 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 9

Src-Bcr-Abl

S1134 AT9283 Size Price

;_‘?Z€;€;^|}~]"C?'ƒ$} 10mg addition to Aurora A and Aurora B, AT9283 was also found to inhibit a number of other kinases including JAK2, N N N NH 50mg ?Z ; |?]}ƒ |}~]"Š?" 'ƒ$ €  *[ € –* O N models and is currently under evaluation in phase I clinical trial. 100mg H HN H N Feed S1134 AT9283

O HEL cells were treated for 3 hours with the indicated concentrations

50 2 4400 20 160 490 of AT 9283. AT 9283 inhibits Jak2-V617F mediated signal transduction at submicromolar concentrations in intact cells. At concentrations of P-STAT5 490 nM the Jak2-V617F inhibition is almost complete and has reached almost omplete and has reached almost background levels (for STAT5 background STAT5 phosphorylation see 4400 nM) Data provided by our customers Dr.Claude Haan and Catherine Rolvering,Universite du Luxembourg S1006 AZD0530 Synonyms: Saracatinib Size Price

AZD0530 is highly selective for Src and Abl kinases against a large range of tyrosine and serine-threonine 5mg O kinases (VEGFR2, FGFR, c-Kit, Aur-3 etc. >5 μM). AZD0530 exerts its activity through ATP competitive and O 25mg O reversible inhibition of the target enzyme. Submicromolar growth inhibition of five of the human cancer cell lines tested with AZD0530(tumor types: colon, prostate, lung, and leukemia) was observed with IC50 values 200mg O HN of 0.2–0.7 μM. Cl N N N Feed O N S1006 AZD0530

IP assay of tyrosine phosphorylation of VDR in the plasma membrane. Primary human †ZZ]|š[ƒ† ?|]"'ƒZŒ~;|")'ƒZ ;› "]?"|;› ƒ|])'ƒ*#$;† ‚ €€† ‚*–|?"")ƒ$;€ anti-phospho-tyrosine was used to detect phosphotyrosines in VDR. A mouse anti-VDR was used to detect immunoprecipitated VDR. Ten % cell extract was set aside as input.

Data provided by our customer Shuxin Han, Kent State University

S1369 Bafetinib Synonyms: INNO-406, NS-187 Size Price

H F Bafetinib (INNO-406) is an orally available, dual Abl/Lyn kinase inhibitor that is up to 55-times more potent than 1mg N N F F imatinib in Bcr-Abl cell lines. Numerous Bcr-Abl mutant proteins (not T315I) are sensitive to INNO-406 in vitro. N 5mg N N N INNO-406 demonstrates specific Src kinase activity against Lyn kinase. HN N 10mg O

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase 9XI(IX'HR

S1033 Nilotinib Synonyms: Tasigna, AMN-107 Size Price

CF3 Nilotinib inhibited the proliferation of Ba/F3 cells expressing p210- and p190-bcr-Abl, or K562 and Ku-812F 10mg

O cells with IC50 values <12 nM. Nilotinib was quantitatively via capture ELISA for its effect on cellular bcr-Abl H 50mg N N N autophosphorylation activity and on Bcr-Abl-dependent cell proliferation IC50 =20–60 nM. Compared with the N N H antiproliferative activity of imatinib , AMN107 was 43times more potent in KBM5 (IC50 of 11.3 versus 480.5 200mg N N nM) and 60 times more potent in KBM7(IC50 of 4.3versus 259.0 nM) cells. S1014 Bosutinib Synonyms:Synonyms: HKI-272 SKI-606 Size Price

25mg N SKI-606 inhibited migration of breast cancer cell lines with IC50 values of 0.1 to 0.3 umol/L; After a 48 h N O N CN treatment with 1 umol/L SKI-606, all the invasioncompetent cell lines were unable to cross the porous 50mg membrane; cell proliferation and survival were unaffected by SKI-606 at concentrations sufficient to block cell O Cl migration and invasion. 100mg HN Feed S1014 Bosutinib Cl O A and B. Sperm were incubated in apacitating medium supplemented with SFK inhibitors and different concentrations of okadaic acid (OA) (panel A) or calyculin-A (panel B), before immunodetection of p-PKA substrates (clone 100G7E). C and D, PVDF membranes used in A and B were stripped as described and used for western blot immunodetection with anti-PY antibodies (clone 4G10).

Data published in J Biol Chem. 2010 Jan 12, provided by our customer Prof. Pablo E. Visconti, Department of Veterinary and Animal Science, University of Massachusetts

S1021 Dasatinib Synonyms:Synonyms: ZMBMS-354825, 252868, Sprycel, AG 1517, BMS354825 Tyrphostin AG 1517 Size Price

Cl An ATP-competitive, dual Src/Abl inhibitor.Dasatinib is a potent inhibitor of imatinib-resistant Kit activation loop 100mg NH mutants and induces apoptosis in mast cell and leukemic cell lines expressing these mutations. Dasatinib N 200mg sensitively inhibits all members of the Src family, including c-Src, Lck, Fyn, and Yes (IC50 < 1.1nmol/L). At O S NH higher concentrations (3 to 28 nmol/L), dasatinib also inhibits the Src kinases Abl, c-Kit, PDGFR, and EphA2. 500mg N

N N a b Feed S1021 Dasatinib N Dasatinib(24h) Untreated OH Dasatinib(48h) Untreated Dasatinib Cytotoxicity by Dasatinib treatment in leukemic cells. 120 30 Œ€– |")'ƒ$ 100 25 Upon treatment, cell viability (a) was calculated as percentage

80 20 with respect to the control vehicle cultures (set to 100% for each cell line) and induction of apoptosis (b) was calculated 60 15 as percentage of Annexin V+/PI+ cells after 48 h of treatment. 40 10 Apoptosis(%) Data from Investigational New Drugs 20 5 October 2010 using our product.

0 0

Cellviability(% of untreatedcultures) EHE JVM-2 JVM-3 MEC-1 MEC-2 BJAB EHEB JVM-2 JVM-3 MEC-1 MEC-2 BJAB

S5002 FTY720 Synonyms: Fingolimod, Gilenia Size Price

NH2 FTY720 is a potent sphingosine-1-phosphate (S1P) receptors agonist with IC50 of 0.137, 10.98 nM for (S)- 200mg HO .HCl and (R)- FTY720-phosphate, respectively and reverses the effects of BCR-ABL kinase. It does not directly 1g target the bcr-Abl kinase, but instead activates phosphatase 2A (PP2A) which is a tumor suppressor that is HO inactivated by Bcr-Abl. FTY720 also mediated antitumor effects in hepatocellular carcinoma (HCC) cells by 2g activating PKC .

S2391 Quercetine Synonyms: Sophoretin, Meletin, Quercetine Size Price

OH 5mg 1(: OH œ€„}?„~}~]"*?$‘)']3$}„}? kinases, mildly inhibited Akt1/2, and slightly affected PKC, p38 and Erk1/2. Quercetin is a naturally-occurring HO O 10mg polar auxin transport inhibitor with IC50 of 0.8, 16.7, 6.1, 11.36 μM for the inhibition of LDH% release, the OH inhibition of TNF-induced PMN-EC adhesion, TNF-induced inhibition of DNA synthesis and proliferation. 50mg OH O

S2202 NVP-BHG712 Page 7

S1264 PD173074 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 9

S1107 PHA-739358 Synonyms:Synonyms: ZMDanusertib 252868, AG 1517, Tyrphostin AG 1517 Page 11

S1490 AP24534 Synonyms: Ponatinib Page 6

 Solutions to Signal Transduction Research /-,/8.+8 Angiogenesis/Tyrosine Kinase

IGF-IR (Insulin-like growth factor 1 receptor)

S1093 GSK1904529A Size Price

F F GSK1904529A, which potently inhibits IGF-IR (IC50= 27 nmol/L) and IR (IC50= 25nmol/L) activities in vitro 10mg HN O

O and in vivo, is a promising candidate for therapeutic use in solid and hematologic cancers. The tumor histologic 50mg N types showing the greatest sensitivity to this compound were Ewing’s sarcoma and multiple myeloma, where N

N IC50s in three of five Ewing’s sarcoma cell lines were <100 nmol/L and IC50s in five of eight multiple myeloma 200mg N HN cell lines were <200 nmol/L. N O N O O N S Feed S1093 GSK1904529A Inhibition of IGF-1 induced IGF-1R phosphorylation Immortalized wild-type mouse embryonic fibroblasts by GSK1904529A. A549 cells were serum-starved O/N were serumstarved for 4 hours,then stimulate with €*<])'_"<]_;Z 100ng/ml IGF-1 for 5 min.Inhibitor was added for the followed by stimulation with 50ng/ml IGF-1. last 1 hour of serum starvation. + IGF-1: positive control; -S: negative control. Data provided by our customers Ursula Broder, Data provided by our customers Ursula Broder, Xuejun Jiang, Memorial Sloan-kettering Cancer Center ETH Zürich - Institute of Biochemistry, Switzerland

S1088 NVP-ADW742 Synonyms:Synonyms: HKI-272ADW742 Size Price

O NVP-ADW742 is an ATP-competitive inhibitor that inhibits IGF-IR autophosphorylation with a cellular IC50 of 10mg

NH 2 "$"$)ŒZ#**€$\†„; !< 50mg N sensitivity of SCLC to etoposide and carboplatin, which are commonly used in the treatment of SCLC. N N 200mg

N HER-2 (Human Epidermal growth factor Receptor 2)

S1019 CI-1033 Synonyms: Canertinib, PD-183805, PD183805 Size Price

F CI-1033 is an orally bioavailable irreversible Pan-ErbB tyrosine kinase inhibitor, targeting EGFR with IC50 of 50mg 0.8, 19 and 7 nM for EGFR, HER-2 and ErbB-4, respectively. It effectively inhibits the growth of esophageal O 100mg HN Cl squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of HN both MAPK and Akt. This inhibition is highly selective for erbB1 (epidermal growth factor receptor), ErbB2, 200mg N ErbB3, and ErbB4 without inhibiting tyrosine kinase activity of receptors such as PDGFR, FGFR, and IR, even at high concentrations. N O N O Feed S1019 CI-1033

Western blot analysis of extracts from EGF, CI-1033 (Selleckchem S1019) treated T47D breast adenocarcinoma cell line using antibodies as indicated.

Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1167 CP-724,714 Size Price

CP-724,714 is an orally available, small molecule, potent HER-2 tyrosine kinase inhibitor under development 1mg O N for the treatment of advanced HER2-overexpressing cancers. It inhibits HER2-chimera phosphorylation with 5mg O HN an IC50 of 15 ng/ml (32 nM), and is >500-fold selective for HER2 relative to other kinases (e.g. EGFR, O N N PDGFR, IGF-1R, VEGFR-2, abl, src). Additionally, CP-724,714 showed a favorable nonclinical toxicity profile 10mg H N with no apparent effects on cardiac tissue.

S1486 AEE788 Synonyms: NVP-AEE 788 Page 3

S1011 BIBW2992 Synonyms: Tovok Page 3

S1028 Lapatinib DitosylateSynonyms: Tykerb, Tyverb, GW-572016 Page 3

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase I1OZI3KZ c-Kit (CD117, also called KIT or C-kit receptor)

S1018 CHIR-258 Synonyms:Synonyms: ZM TKI-258, 252868, Dovitinib, AG TKI258 1517, Tyrphostin AG 1517 Page 7

S1363 Ki8751 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 8

S1064 Masitinib Synonyms:Synonyms: ZM AB1010, 252868, Masivet AG 1517, Tyrphostin AG 1517 Page 6

S1244 MP-470 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 8

S1220 OSI-930 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 8 S1178 BAY 73-4506Synonyms:Synonyms: ZM Regorafenib 252868, AG 1517, Tyrphostin AG 1517 Page 8

c-Met (mesenchymal-epithelial transition factor)

S1114 JNJ-38877605 Size Price

F F N N JNJ-38877605 is an orally bioavailable, highly specific c-Met inhibitor (selective over other 229 kinases 10mg N N N tested). This agent inhibits c-Met and Phospho-Met with IC50 at 4 nmol/L and 50 nmol/L, respectively. In 50mg addition, JNJ-38877605 induces regression of U87-MG xenografts in vivo. N N 200mg S1068 PF-2341066 Synonyms: ZM Crizotinib 252868, AG 1517, Tyrphostin AG 1517 Size Price

HN PF-2341066 is Inhibitor of the catalytic activity of c-Met kinase and the NPM-ALK fusion protein. PF-2341066 5mg inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (mean IC50 value=24 nM). 10mg N PF-2341066 potently inhibited cell proliferation, which was associated with G1-S–phase cell cycle arrest and N induction of apoptosis in ALK-positive ALCL cells (IC50 values=30 nM) but not ALK-negative lymphoma cells. 50mg N Feed NH 2 p-cMET S1068 PF-2341066 O (R) cMET Western blot analysis of p-cMet, c-Met, p-MAPK, MAPK, p-Akt, Akt. Cl Cl p-MAPK PF-2341066 treated T47D breast adenocarcinoma cell line using antibodies as indicated. MAPK F Produced Independently by our customer Dr.Zhang, Tianjin Medical University p-AKT AKT

HGF (ng/ml) 10 10 10 10 10 0

PF2341066(nM) 0 0.1 1.0 10.0 100.0 0 S1316 AMG-208 Size Price

O N AMG 208 is a small molecule inhibitor of c-Met, which inhibits both ligand-dependent and ligand-independent 10mg

O c-Met activation. It is being investigated as a cancer treatment. 50mg N N N N 200mg S1094 PF-04217903 Synonyms: HKI-272 Size Price

N PF-04217903 is an orally bioavailabe, small-molecule MET tyrosine kinase inhibitor with potential 5mg antineoplastic activity. PF-04217903 demonstrates exquisite kinase selectivity. On the basis of the percent HO N 10mg inhibition or IC50 values generated from each of these screens, PF-04217903 was estimated to be>1000-fold N N N N selective for c-Met compared with each of the other kinases included in these collective screening assays. 50mg N N p-cMET Feed S1068 PF-04217903 cMET Western blot analysis of p-cMet, c-Met, p-MAPK, MAPK, p-Akt, Akt. p-MAPK PF-04217903 treated T47D breast adenocarcinoma cell line using antibodies as indicated. MAPK Produced Independently by our customer Dr.Zhang, Tianjin Medical University p-AKT

AKT

HGF (ng/ml) 10 10 10 10 10 0

Pf04217903 (­M)0 0.1 1.0 10.0 20.0 0

 Solutions to Signal Transduction Research I3KZ,2: Angiogenesis/Tyrosine Kinase

S1070 PHA-665752 Size Price

H Cl N O PHA-665752 was identified as a small molecule, ATP-competitive, active site inhibitor of the catalytic activity 10mg S H O O N of c-Met kinase (Ki of 4 nM, IC50 of 9 nM). PHA-665752 also exhibited >50-fold selectivity for c-Met compared Cl 50mg N with a panel of diverse tyrosine and serine-threonine kinases. In cellular studies, PHA-665752 potently O inhibited HGF-stimulated and constitutive c-Met phosphorylation, as well as HGF and c-Met-driven 200mg N phenotypes such as cell growth of a variety of tumor cells. S1112 SGX-523 Size Price

S N N SGX-523, an orally bioavailable small molecule, specifically binds to c-Met protein, or hepatocyte growth factor 5mg N N N receptor (HGFR), preventing binding of hepatocyte growth factor (HGF) and disrupting the c-Met signaling 10mg pathway. This agent has shown exceptional selectivity for the cMET receptor tyrosine kinase over more than N 200 protein kinases. SGX-523 may induce cell death in tumor cells expressing c-Met in vitro and in vivo. 25mg N

Synonyms: PKI-SU11274 S1080 SU11274 Size Price

Ÿ<**'Z}~]"*'•"$")Œ$ 5mg N H inhibitor did not affect other tyrosine kinase oncoproteins, including BCR-ABL, TEL-JAK2, TEL-PDGF_R, or N 25mg O TEL-ABL. Inhibition of the Met kinase activity by SU11274 led to time- and dose-dependent reduced cell Cl N N S growth. SU11274 belongs to a class of small molecule RTK inhibitors that exert their activity by competing for 200mg O O O the Mg-ATP complex binding pocket, which results in inhibition of kinase activity and subsequent downstream HN signaling. Feed S1080 SU11274 p-cMET

cMET Western blot analysis of p-cMet, c-Met, p-MAPK, MAPK, p-Akt, Akt. SU11274 treated T47D breast adenocarcinoma p-MAPK cell line using antibodies as indicated. MAPK Produced Independently by our customer Dr.Zhang, Tianjin Medical University P-AKT

AKT

HGF (ng/ml) 10 10 10 10 10 0

SU11274(­M)0 0.1 1.0 10.0 20.0 0 S1361 MGCD-265 Page 8

S1111 Foretinib Synonyms: ZM XL880, 252868, GSK1363089, AG 1517, GSK089, Tyrphostin EXEL-2880 AG 1517 Page 9

S1005 Axitinib Synonyms: AG-013736 Page 10

FLT-3 (fms-like tyrosine kinase receptor-3)

S1043 Tandutinib Synonyms:Synonyms: HKI-272MLN518, CT53518 Size Price

N N In cell-based assays tandutinib inhibited FLT3, PDGFR, and KIT with IC50 values of 95-122 ng/mL, but had 25mg N H no significant effect against a broad range of other kinases. In Ba/F3 cells expressing various FLT3-ITD N N 100mg N O mutants, tandutinib inhibited IL-3-independent growth and FLT3-ITD auto-phosphorylation with IC50 values of O O O 6-17 ng/ml. Tandutinib has a very limited spectrum of activity outside the type III receptor kinase family. 200mg

S1526 AC220 Size Price

O AC220 is a uniquely potent and selective FLT3 inhibitor with IC50 of 0.56 ± 0.3 nM and >10 mM for MC4-11 10mg N and A375, respectively. It exhibits low nanomolar potency in biochemical and cellular assays and exceptional O 50mg N kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The S data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to 200mg O N O AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for N N N H H a clinical FLT3 inhibitor. S2158 KW 2449 Size Price

HN N KW-2449, a multi-kinase inhibitor of FLT3 (IC50 at 6.6pM), Abl(IC50 at 14pM), Abl-T315I and Aurora kinase. 10mg O KW-2449 potently and selectively inhibits the growth of leukemia cells harboring constitutively activated FLT3 25mg kinase both in vitro and in vivo. On the other hand, KW-2449 had little effect on PDGFR, EGFR, and various N serine/threonine kinases even at a concentration of 1 uM. Among various serine/threonine kinases examined, 50mg KW-2449 inhibited Aurora A kinase with IC50 of 48 pM and Aurora B kinase with the equivalent potency. N H

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Angiogenesis/Tyrosine Kinase ,2:'21<*'+:'XKIKVZUX./,

S1003 ABT-869 Synonyms:Synonyms: ZM Linifanib, 252868, AL-39324, AG 1517,RG3635 Tyrphostin AG 1517 Page 6

S1490 AP24534 Synonyms:Synonyms: ZM Ponatinib 252868, AG 1517, Tyrphostin AG 1517 Page 6

S1018 CHIR-258 Synonyms:Synonyms: ZM TKI-258, 252868, Dovitinib, AG TKI258 1517, Tyrphostin AG 1517 Page 7

S1119 XL184 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 9

S1134 AT9283 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 11

ALK (anaplastic lymphoma kinase)

S1108 NVP-TAE684 Synonyms: TAE684 Size Price

Cl N O HN N NH NVP-TAE684 is a highly potent and selective small molecule ALK inhibitor, which blocked the growth of 5mg S O O ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM. NVP-TAE684 treatment N 10mg resulted in a rapid and sustained inhibition of phosphorylation of NPM-ALK and its downstream effectors and N subsequent induction of apoptosis and cell cycle arrest. 200mg

N S1476 SB 525334 Size Price

^]]??<***}|;Œ]Z‚}ƒ|}~]" <$?'ƒ$ 5mg NH N €;Œ]Z N 50mg of the Smad transcription factors and subsequent gene activation. N N 100mg

VDA (Vascular Disrupting Agent)

Synonyms: AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan S1537 DMXAA(ASA404) Size Price O DMXAA is a tumor-vascular disrupting agent with an IC50 of 9.46 ± 1.7 nM. It attacks the blood supply of a 5mg cancerous tumor to cause tumor regression. It has a striking antivascular and in some cases curative effect in 25mg O experimental tumors. The latter involving the release of further vasoactive agents, such as serotonin, tumour OH necrosis factor, other cytokines, and nitric oxide from host cells. 100mg O S1176 NPI-2358 Synonyms: Plinabulin Size Price

O NPI-2358 is a novel vascular disrupting agent acting on tubulin dimerization that destabilizes tumor vascular 10mg NH N endothelial cells and has cytotoxic activity (IC50 values of 10-15nM). NPI-2358 selectively induces tumor 50mg HN NH vascular collapse and tumor regression in murine tumor models and potentiates other oncology agents. Preclinical data suggest NPI-2358 may have advantages in terms of safety profile and activity. 200mg O

ETA-receptor (Endothelin receptor type A)

S1456 Zibotentan Synonyms: ZD4054 Size Price

O O Zibotentan is an orally administered, potent and specific ETA-receptor antagonist (IC50 = 21 nM). In vitro, 10mg O H N O N Zibotentan has been shown to compete with 125I-ET-1 for binding to the cloned human ETA-receptor with an N S N 50mg N IC50 value of 21 nM. No binding to the ETB receptor was observed with concentrations of zibotentan in excess *")'$*€€€*** 200mg N activation of the ETA receptor and which promote tumor survival, growth and progression. HIF (Hypoxia-inducible factor)

S1233 2-Methoxyestradiol Synonyms: 2-ME2 Size Price OH 2-Methoxyestradiol targets on both the tumor cell and endothelial cell compartments by inducing apoptosis in 50mg H rapidly proliferating cells and inhibiting blood vessel formation at several stages in the angiogenic cascade. O 100mg Moreover, the ability of 2-Methoxyestradiol(2ME2) to inhibit metastatic spread in several models adds to its H H therapeutic value for cancer treatment at various stages of the disease. 300mg HO

 Solutions to Signal Transduction Research 9_Q:OKQOTGYK Angiogenesis/Tyrosine Kinase

Syk (Spleen tyrosine kinase)

S2194 R406 Size Price

R406 is an orally available spleen tyrosine kinase inhibitor with an IC50 of 41 nM. R406 blocked 10mg 1(: O O F O Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated N O OH 50mg S activation of B lymphocytes. R406 treatment ameliorated joint inflammation in a number of rodent models of O N N N N N O H H H O rheumatoid arthritis and also blocked JNK-mediated gene expression in human synoviocytes. 200mg S1533 R406(free base) Size Price

O R406 is an orally available spleen tyrosine kinase inhibitor with a Ki of 30 nM. R406 blocked Syk-dependent 10mg O F O FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B N 50mg lymphocytes. R406 was selective as assessed using a large panel of Syk-independent cell-based assays O N N N N N O representing both specific and general signaling pathways. 200mg H H H

S2206 R788 Synonyms: FosD, Tamatinib Fosdium Size Price O Na+ -O O- Na+ P R788 is a selective Syk inhibitor with an IC50 of 41 nM. R788 exhibits inhibitory activity against SYK but also 1mg 1(: O H H €*$}‚Z‚‘‘ O N N N N N O 5mg blocked BCR-mediated Ag presentation, thus broadly interrupting the humoral contributions to T cell-driven N O F O autoimmunity. 50mg O

Tie2 kinase

S1119 XL184 Page 9

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Cell Cycle/Checkpoint Pathway

The term ‘cell-cycle checkpoint’ refers to mechanisms by which the cell actively halts progression through the cell cycle until it can ensure that an earlier process, such as DNA replication or mitosis, is complete. The cell cycle and cell cycle-associated proteins play essential roles in cell fate, including cell replication, cell death, and cell function.

At present, the most well-characterized cell-cycle proteins are the serine/threonine kinases Cdk1 and Cdk2 and proteins acting as inhibitors of these kinases, p21 and p27. Rho in this definition functions as a molecular switch in cellular processes such as cell morphogenesis, adhesion, migration and cell cycle progression including cytokinesis. DNA polymerases are rarely the actual, final target for chemotherapeutics, the biological activity of some nucleoside-based drugs absolutely depends upon DNA polymerases to incorporate them into DNA. The purine- and pyrimidinebased nucleoside antimetabolites are frontline therapies for a large number of different tumors. DNA topoisomerases are critical for DNA replication because of their ability to unwind DNA and relieve superhelical stress in the DNA enzyme potently kills replicating cells.

A role for novel cell-cycle proteins in podocyte biology. Peter M. Price. Kidney International. 2010(77), 660 – 661 Introduction to Cancer Chemotherapeutics. Donna S. Shewach. Chem. Rev. 2009;109 (7):2859–2861



Papers Using Selleck Products

S1109 BI 2536 Targeting Mitotic Exit Leads to Tumor Regression In Vivo: Modulation by Cdk1, Mastl and the PP2A/B55a,d Phosphatase. Eusebio Manchado et al. Cancer Cell, 2010(18):641–654

Small Molecule Kinase Inhibitor Screen Identifies Polo-Like Kinase 1 as a Target for Neuro- blastoma Tumor-Initiating Cells. Natalie Grinshtein et al. Cancer Res, 2011(71):1385-1395

S1532 AZD7762 Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells. William Brazelle et al. PLoS ONE, 2010; 5(12): e14335.

 Cell Cycle/Checkpoint 85)1621)*1

ROCK

S1573 Fasudil HCl Synonyms: HA-1077, AT-877 Size Price 10mg O €[~€‚š~}~]"*"$) S N 2+ N O M. It is also a Ca antagonist and vasodilator. It also inhibits proliferation of vascular smooth muscle cells. 50mg NH HCl 100mg

S1474 GSK429286A Size Price H O N H GSK429286A is a cell-permeable, selective inhibitor of Rho-associated kinase (ROCK). ROCK inhibitors have 2mg N N been found to prevent apoptosis, as well as to enhance the survival and cloning efficiency of dissociated O F N 50mg H human embryonic stem (ES) cells without affecting their self-renewal properties or pluripotency. Because of GSK429286A's specificity, this reagent may be useful in assessing the cellular roles of individual ROCK F F F isoforms. S1049 Y-27632 Size Price

N O ~  #? | 'M?"")'ƒ$ 10mg N |_$"/$]’‘]$#/?$#’?"")'ƒ}~]"*?$?/"$])'$‘/"$)'€ H 50mg rabbit tissues respectively. The IC50 value of Y-27632 was 1 ± 0.2 μmol/L for the inhibition of shape change H by U46619. 200mg NH2 PLK (Polo-like kinase)

S1109 BI 2536 Size Price

N O BI 2536 is a small molecule compound with potential anti-neoplastic activities. BI 2536 binds to and inhibits 5mg O N O N N PLK1 (with IC50of 0.83 nM), resulting in mitotic arrest, disruption of cytokinesis, and apoptosis in susceptible H 10mg tumor cell populations. This compound showed a more than 1000-fold selectivity relative to a panel of 63 other N N N H protein kinases, but it also affected the activities of PLK2 at an IC50 of 3.5 nM and, to a slightly lesser extent, 50mg the activity of PLK3 (IC50 9.0 nM). S2193 GSK461364 Size Price O N S N 10mg 1(: NH2 GSK 461364 is a potent small molecule PLK1 inhibitor with a Ki of 2.2 nM. GSK461364 is an ATP-competitive F O F inhibitor of PLK1 and forms a rapidly reversible complex with PLK1. It has a 400-fold greater potency for PLK1 F 50mg than for PLK2 and PLK3. It is > 100-fold selective with respect to PLk2, PLK3, and 48 other kinases tested. N N 200mg S1485 HMN-214 Synonyms: IVX-214 Size Price

O O O HMN-214 is a potent PLK1 inhibitor (an average cell IC50 of 118 nM). HMN-176 interferes with PLK1, but does 10mg S O N N not appear to directly inhibit PLK1. Instead, it alters its spatial distribution, resulting in cell cycle arrest at the 50mg G2–M phase, with destruction of the spindle polar bodies followed by DNA fragmentation. Drug-resistant cell O lines showed low crossresistance to HMN-176. In human tumor xenografts, there was a broad spectrum of 200mg antitumor activity. S1362 ON-01910 Synonyms: Estybon Size Price

O O O ON-01910 is a non-ATP-competitive small molecule Plk1 inhibitor with an IC50 of 9 nM. It induces mitotic 10mg S arrest of tumor cells characterized by spindle abnormalities leading to their apoptosis. In vivo, this compound 50mg O O did not exhibit hematotoxicity, liver damage, or neurotoxicity, and was a potent inhibitor of tumor growth in a NH variety of xenograft models. ON01910 showed strong synergy with several chemotherapeutic agents, often 200mg O O inducing complete regression of tumors. ONa CDK (Cyclin-dependent kinase)

S1524 AT7519 Synonyms: AT 7519 SizeSize Price Price

AT7519 is a novel small molecule multi-cyclin-dependent kinase inhibitor. It selectively binds to and inhibits 5mg Cl Cl CDKs, which may result in cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. 10mg O NH O CDKs are serine/theronine kinases involved in regulation of the cell cycle and may be overexpressed in some NH types of cancer cells. N 25mg HN N H

 Solutions to Signal Transduction Research )*1 Cell Cycle/Checkpoint

S1572 BS-181 HCl Size Price

BS-181 is a selective cyclin-dependent kinase inhibitor with an IC50 of 21 nM for the inhibition of 10mg

HN CDK-activating kinase. Testing of other CDKs as well as another 69 kinases showed that BS-181 only 25mg N N ~ )'Z~ ?]*|}~]"‘‘" H N 2 N N nM) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle H 50mg arrest and apoptosis to inhibit the growth of cancer cell lines. HCl

S2386 Indirubin Size Price

H N }€?}~]"*€]'"$_)'$} 5mg 1(: O ~ ]?€$;;'„ZŒ~$}€ O *$}€€\'^€€ 25mg HN inflammatory agents and carcinogens. 100mg

S1230 Flavopiridol Synonyms: HMR-1275, Alvocidib, L868275 Size Price

OH O Flavopiridol inhibited rhabdoid cell growth (IC50-200nmol/L) , induced G1 and G2 arrest, and apoptosis in vitro 10mg in a concentration-dependent manner. These effects were correlated with the down-modulation of cyclin D1, HO O 25mg H HO up-regulation of p21, and induction of caspase 3/7 activities. Flavopiridol (at 7.5 mg/kg) significantly inhibited Cl the growth of xenografted rhabdoid tumors, and its effect was correlated with the induction of p21 and N 50mg down-modulation of cyclin D1.

S1249 JNJ-7706621 Size Price

O JNJ-7706621 blocked proliferation of cancer cells regardless of their p53, retinoblastoma or P-glycoprotein 1mg status and induced cell death by activating apoptosis; delayed progression through G1 and arrested the cell S NH 5mg F cycle at the G2/M phase; decreased CDK1 kinase activity, altered CDK1 phosphorylation status and blocked H2N O N N signaling to downstream substrates of CDKs; reduced histone H3 phosphorylation; inhibited Aurora kinase. In 10mg N *}~]"|)ŒƒŠ[Œ}~]" "$‘#Z[~#}~]" "$‘_Z„~?}~]" "$$ H N O F 2 Histone H3 Feed S1249 JNJ-7706621

p-Histone H3 Western blot analysis of p-Histone H3, Histone H3, p-Aurora A/B/C, Aurora A ;€;$"")'¦\¦"##$

p-Aurora A/B/C Produced Independently by our customer Dr.Zhang, Tianjin Medical University 0μM 0.001μM 0.01μM 0.1μM 1μM 10μM JNJ-7706621

S1116 PD0332991 Size Price

PD0332991 is an orally available pyridopyrimidine-derived CDK inhibitor with potential antineoplastic activity. 5mg HN O €**~ <|}~]"Z"$")Œƒ~ #|}~]"Z"$"#)ŒƒZ 10mg N having no activity against a panel of 36 additional protein kinases. Therapeutic doses of PD0332991 cause N N elimination of phospho-Rb and the proliferative marker Ki-67 in tumor tissue and downregulation of genes 25mg under the transcriptional control of E2F. N N N O H Feed S1116 PD-0332991

Serum-deprived T98G glioma cells are restimulated with €|^ƒ€)'„ "??__ CDK4/6 inhibitor.

Data provided by our customer Pierre Roger, IRIBHM,ULB,BRUSSELS(Belgium).

S1487 PHA-793887 Size Price

H N 5mg N PHA-793887 is a novel pan-cdk inhibitor, including CDK1, CDKT2, CDK4, CDK5, CDK7, and CDK9 with IC50 O in the 5 to 140 nM range. It is inactive against other 34 kinases representative of all kinase families, in N 10mg HN particular c-Abl, c-Kit, lck, and TRKA with IC50＞10 mM. It shows anti-proliferative activity against several O solid tumor cell lines, with IC50＜1 mM. In these cells, it is able to inhibit Rb phosphorylation and expression 50mg N of S-phase cyclins, such as cyclin A. S1153 Roscovitine Synonyms: CYC202, Seliciclib Size Price

Roscovitine is a potent and selective inhibitor of CDKS. Roscovitine inhibits p34 cdc2/cyclin B (IC50 = 0.65 10mg μM), p33 CDK2/cyclin A (IC50 = 0.70 μM), p33 CDK2/cyclin E (IC50 = 0.70 μM), and p33 cdk2/p35(IC50 = 25mg HN 0.20 μM) by competing for the ATP binding domain of these kinases. Roscovitine exhibits very low sensitivity towards related kinases, such as Erk1 and Erk2 (IC50 = 34 μM and 14 μM, respectively). Roscovitine displays N N 50mg HO increased anti-mitotic activity at the G1/S and G2/M phases of the cell cycle. N N N H

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Cell Cycle/Checkpoint )*1:UVUOYUSKXGYK3OIXUZ[H[RK

S1145 SNS-032 Synonyms: BMS-387032 Size Price

SNS-032 is a small-molecule CDK inhibitor for the treatment of B-cell malignancies and advanced solid 5mg NH H tumors. SNS-032 is a specific and potent inhibitor of CDK2, 7 and 9 which induces cell cycle arrest and O S N S apoptosis in tumor cell lines. It was shown to inhibit in vitro angiogenesis and prostaglandin E2 (PGE2) 10mg N O production, both strongly associated with tumorigenesis. Phase I clinical trials support the safety and N 50mg tolerability of SNS-032 as evaluated in dose-escalation studies.

Topoisomerase

S1208 Adriamycin Synonyms: Doxorubicin, Rubex Size Price

OH H O Adriamycin is an anthracycline antibiotic and is used in cancer chemotherapy. It inhibits the progression of the 25mg O O OH O NH2 enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Doxorubicin stabilizes the 100mg topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix OH OH O OH O from being resealed and thereby stopping the process of replication. It has an inhibitory effect on MCF-7 and 200mg .HCl ' ;'^?}~]"*)'Z$ S1288 Camptothecine Size Price

O 500mg O N Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme topoisomerase I (topo I). It was isolated from the bark and stem of Camptotheca acuminata, a tree native in China. Two CPT analogues O 1g HO N have been approved and are used in cancer chemotherapytoday, topotecan and irinotecan. 5g

S2217 Irinotecan HCl Trihydrate Synonyms: CPT 11, Camptosar, Campto, Irinotecan Size Price

O

H O N 1(: 2 O }}}~]"*]$‘]$)'*Œ† 100mg and HT-29 cells, respectively. As a Topo I inhibitor, Irinotecan inhibits the religation step of the enzyme’s O N O OH N N normal action, inducing single stranded DNA breaks. Irinotecan is activated by esterases to produce the 200mg O HCl H2O activated metabolite and has been reported to be associated with cleavage of PARP in colon carcinoma cells. H2O 1g

Synonyms: Eposin, Vepesid, VP-16, Toposar S1225 Etoposide Size Price OH O O Etoposide caused an increase in the mean fluorescence intensity of FasR in both subclones, and an induction 25mg O H O of FasL in the ES subclone. However, no change in the numbers of apoptotic cells induced by etoposide was O O 100mg H H observed when FasR was blocked by an antagonist anti-Fas antibody, nor was an agonist anti-Fas antibody O O O H O OH alone cytotoxic to the subclones or enhanced the cytotoxic effect of etoposide. H 500mg OH S1198 Irinotecan Synonyms: Camptosar Size Price

O Irinotecan is an inhibitor of topoisomerase I and is activated by hydrolysis to SN-38. The inhibition of 100mg N O topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and 200mg transcription. Its main use is in colon cancer, particularly in combination with other chemotherapy agents. The O N O HO N N –*\?‘*Š}~]"€]$‘)' 1g O *Œ†]$)'*[_“\?‘}~]"€‘$]'*Œ†<$]"'* HT-29 cells.

S2485 Mitoxantrone Size Price

H N Mitoxantrone is a type II topoisomerase inhibitor with IC50 of 2.0 μM, 0.42 mM for HepG2 and MCF-7/wt cells, 100mg 1(: OH O HN OH respectively. It disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells. It is used in the 200mg treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin’s lymphoma. It was also shown to improve the survival of children suffering from first relapse of OH O HN OH 250mg N H acute lymphoblastic leukaemia. S1231 Topotecan HCl Synonyms: Hycamtin, NSC 609699 Size Price

O 50mg Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble N O N derivative of camptothecin. It is used to treat ovarian cancer and lung cancer, as well as other cancer types. 100mg O N OH HO 200mg HCl Microtubule

S2209 Vinflunine Tartrate Size Price

F 1(: F Vinflunine Tartrate is a new microtubule inhibitor with IC50 of 18.8 nM. Vinflunine suppressed the rate of 10mg N OH |}~]" "$<)'ƒ$š**Z€€*'Z€* N O COOH 50mg N HOOC microtubular network of interphase cells and formation of paracrystals, generally required 3- to 17-fold higher H H O OH O O concentrations of vinflunine than the other vinca alkaloids. O O N HOH O 200mg

 Solutions to Signal Transduction Research 3OIXUZ[H[RK Cell Cycle/Checkpoint

S2195 CYT997 Size Price O

N NH 1(: H CYT997, a synthetic small molecule optimized for antiproliferative activity in a panel of cell-based assays, in 10mg O which the compound shows an IC50 of between 1 and 100 nmol/L across a panel of cancer cell lines. The € • * €€ }~]" * ?)Œ$ ~__ € * NN increase of cells in the G2/M phase of the cell cycle. Caspase-3 activation is also observed in cells treated with N N H CYT997 along with the generation of PARP.

S1165 ABT-751 Size Price

O H N S ABT-751 is a bioavailable antimitotic sulfonamide agent that binds to the colchicine-binding site on 10mg O HN N beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. O 50mg ABT-751 is not a substrate for the MDR transporter and is active against cell lines resistant to vincristine, doxorubicin, and cisplatin. This agent also disrupts tumor neovascularization, reducing tumor blood flow and 200mg OH so inducing a cytotoxic effect. S2284 Colchicine Size Price

O 10mg O Colchicine inhibits microtubule polymerization by binding to tubulin. Since one of the defining characteristics O of cancer cells is a significantly increased rate of mitosis, this means that cancer cells are significantly more O O 25mg H vulnerable to colchicine poisoning than are normal cells. However, the therapeutic value of colchicine against N H O cancer is limited by its toxicity against normal cells. 50mg S1148 Docetaxel Synonyms: Taxotere Size Price

HO O OH Docetaxel is a semi-synthetic, second-generation taxane, with anti-neoplastic application for the treatment of 100mg

O breast, ovarian, and non-small cell lung cancer. Docetaxel binds to and stabilizes tubulin, thereby inhibiting 250mg O microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death. The overall cells O OH O Ac O O mean IC50 for docetaxel treatment was 4.67 nM,This agent also inhibits pro-angiogenic factors such as VEGF O 500mg O N H OH and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. S1297 Epothilone A Synonyms: Ellence, Pharmorubicin, Epirubicin Ebewe Size Price

S N Epothilone A is a new kind of microtubule function inhibitor with an IC50 of 4.4 nM for tubulin polymerization 1mg and cytotoxicity. It competitively inhibits [3H]-paclitaxel binding to microtubules. It prevents cancer cells from O OH dividing by interfering with tubulin. It exhibits kinetics similar to paclitaxel by inducing tubulin polymerization in 5mg O O vitro and producing enhanced microtubule stability and bundling in cultured cells. Epothilone A exhibits a greater cytotoxicity against P-glycoprotein-expressing multidrug resistant (MDR) cells (IC50 = 20 nM). OH O S1364 Epothilone B Synonyms: EPO906, EpoB, Patupilone Size Price

S N Epothilone B is a new kind of cancer drugs and microtubule function inhibitor with an IC50 of 3.5 nM. 1mg Epothilone B suppressed microtubule dynamics in a concentration-dependent manner coincident with mitotic O OH 5mg O O block. At the IC50, 80% of the cells had nearly complete stabilization of microtubule dynamics, and no anaphase or telophase figures were observed. OH O S1150 Paclitaxel Synonyms: Onxol, Taxol, Nov-Onxol Size Price O

O O O OH Paclitaxel is a microtubule polymer stabilizer with an IC50 of 0.1 pM for human endothelial cells. It selectively 100mg O N inhibits the proliferation of human endothelial cells at ultra low concentrations (0.1-100 pM), while it inhibits H O H HO O O non-endothelial type human cells with IC50 1-10 nM. The selectivity of paclitaxel inhibition of cell proliferation 500mg OH O O O is also species specific. Paclitaxel blocks cells in G2/M, and this may result in a schedule-dependent effect on 1g paclitaxel cytotoxicity. S1241 Vincristine Sulfate Synonyms: leurocristine, Oncovin, Vincasar PFS, Vincrex Size Price

HO N OH O Vincristine Sulfate is a kind of microtubule function inhibitor with IC50 of 10.4±1.1, 28.1±3.4, 22.4±2.1 μM for 10mg S O HL-60, Bel7402, HO-8910, respectively. Vincristine binds irreversibly to microtubules and spindle proteins in HN N OH 25mg O H S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells O H O O in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic N OH 50mg H O O O O AMP, and glutathione metabolism. S1240 Vinflunine Synonyms: Javlor Size Price

F F Vinflunine is a novel fluorinated Vinca alkaloid currently and tubulin assembly inhibitor with an IC50 of 18.8 nM 25mg

N for mitotic accumulation. t is interesting that the IC50 and IC70 concentrations suppressed microtubule 50mg N O dynamics, slowed down mitotic progression from metaphase to anaphase, and induced a postmitotic G1 N H H O arrest. This G1 arrest was associated with an increase in p53 and p21 expression and with their nuclear O O 100mg O translocation. O N HOH O

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Antimetabolites

S1156 Capecitabine Synonyms: Xeloda Size Price

OH HO 100mg O As a prodrug, capecitabine is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU); subsequently, 5-FU is metabolized to two active metabolites, FdUMP and FUTP by both tumor cells and O NNO 200mg normal cells. Capecitabine is a chemotherapy drug that is given as a treatment for many types of cancer, O N H including bowel cancer, breast cancer, stomach cancer and oesophageal cancer. F 1g S1199 Cladribine Synonyms: Leustatin, 2-chlorodeoxyadenosine Size Price Cl Cladribine is a drug used to treat hairy cell leukemia and multiple sclerosis. As a purine analog, it is a synthetic 25mg NN anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine OH 50mg O and thus inhibits the enzyme adenosine deaminase, which interferes with the cell’s ability to process DNA. It H2N N is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side OH 100mg N effects and results in little non-target cell loss. S1218 Clofarabine Synonyms: Clolar, Evoltra Size Price

NH2 10mg N N Clofarabine is a second generation purine nucleoside analog. It is phosphorylated intracellularly, which inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase, resulting in inhibition Cl N N 25mg of DNA repair and synthesis of DNA and RNA. Clofarabine also disrupts mitochondrial function and membrane O F integrity, resulting in the release of pre-apoptotic factors, including cytochrome C and apoptotic-inducing OH 50mg HO factor, which activate apoptosis.

S1200 Decitabine Synonyms: Dacogen, 5-aza-2'-deoxycytidine Size Price

N NH2 O Decitabine is a cytidine antimetabolite analogue with potential antineoplastic activity. Decitabine incorporates 25mg N N into DNA and inhibits DNA methyltransferase, resulting in hypomethylation of DNA and intra-S-phase arrest of O 50mg DNA replication. The use of decitabine could result in activation of several tumor suppressor genes and HO induction of differentiation of undifferentiated cells. HO 100mg S1299 Floxuridine Synonyms: Fluorodeoxyuridine Size Price F Floxuridine is an oncology drug that belongs to the class known as antimetabolites. The drug is most often 100mg O O N used in the treatment of colorectal cancer. Floxuridine, an analog of 5-fluorouracil, is a fluorinated pyrimidine. HO NH 200mg HO O 1g S1229 Fludarabine Phosphate Synonyms: Fludara Size Price

Inside the cells rephosphorylation occurs which leads to fuoroadenine arabinoside triphosphate (F-ara-ATP), 50mg N O N the major cytotoxic metabolite of F-ara-A. This metabolite inhibits several key processes necessary for the H2N OPO3H2 DNA replication. Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by 100mg NN OH increased expression of ICAM-1 and IL-8 release. Fludarabine did not affect the growth of ovarian cancer cell HO 200mg F lines, whereas it induced a marked and dose-dependent inhibition of proliferation in melanoma cell lines. Synonyms: Fludara Size Price S1491 Fludarabine N NH2 Fludarabine inhibits several key processes necessary for the DNA replication, ribonucleotide reductase, DNA 50mg N N primase, DNA polymerase, 3’-5’ exonuclease activity of DNA polymerase d and e and DNA ligase I. O 100mg N Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased F expression of ICAM-1 and IL-8 release. Fludarabine did not affect the growth of ovarian cancer cell lines, HO OH 200mg HO whereas it induced a marked and dose-dependent inhibition of proliferation in melanoma cell lines.

S1149 Gemcitabine HCl Synonyms: Gemzar Size Price

O N NH2 Gemcitabine is converted intracellularly to the active metabolites difluorodeoxycytidine di- and triphosphate 25mg O N (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool HCl 100mg available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and HO F HO F apoptosis. Gemcitabine inhibits proliferation BxPC-3 pancreatic cancer cell line with IC50 of 0.06 μM. 300mg

S1135 Pemetrexed disodium Synonyms: Alimta, LY-231514 Size Price

O ONa O 10mg O ONa Pemetrexed disodium (Alimta, Rolazar, Tifolar, MTA) is a thymidylate synthase, dihydrofolate reductase and N N H2N H O glycinamide ribonucleotide formyltransferase inhibitor with an IC50 of 25, 34, 220 nM for CCRF-CEM, 50mg HN HN GC3/cl1, HCT-8, respectively. 200mg S1192 Raltitrexed Synonyms: Tomudex Size Price

N Raltitrexed is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase. 25mg O S NH HO NH Raltitrexed is chemically similar to folic acid. It works by inhibiting Dihydrofolate reductase, an enzyme used in N O 50mg O the synthesis of tetrahydrofolate, thereby preventing the synthesis of thymidylate. Raltitrexed inhibits L1210 O OH cell growth in culture IC50 = 9 nM, which is one of the strongest antimetabolites in use. 100mg  Solutions to Signal Transduction Research :KRUSKZGYK*4'84' Cell Cycle/Checkpoint

Telomerase

S1186 BIBR1532 Size Price

O BIBR1532 is a selective telomerase inhibitor. This reagent inhibits the in vitro processivity of telomerase in a 10mg dose-dependent manner, with IC50 of 93 nM. The selectivity of BIBR1532 was assessed in a panel of DNA (E) N 50mg H and RNA polymerases, showing that none of these enzymes was inhibited in concentrations up to 100 uM. COOH BIBR1532 has a direct cytotoxic effect on leukemia cells but not in normal hematopoietic stem cells. 200mg DNA/RNA

S1521 Carmustine Synonyms: Gliadel, BCNU, NSC-409962, Becenun Size Price

O Carmustine(BiCNU) is a cell-cycle phase nonspecific alkylating antineoplastic agent with ED50 ranging from 100mg Cl Cl 5.0 μM to 11.9 μM. It is used in the treatment of several types of brain cancer (including glioma, glioblastoma N N multiforme, medulloblastoma and astrocytoma), multiple myeloma and lymphoma (Hodgkin’s and 500mg H non-Hodgkin). Three lines with O6-AGT activity below 25 fmol/mg protein had carmustine ED50 values N 1g O ranging from 5.0 μM to 11.9 μM.

S1648 Cytarabine Synonyms: Ara-C, Cytosine Arabinoside, Cytosar-U Size Price

H2N O ~ * *€$ } 10mg N OH chemotherapy agent used mainly in the treatment of hematological malignancies. Because the arabinose O 25mg sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. This agent also inhibits DNA polymerase, resulting in a decrease in DNA replication HO 100mg OH and repair.

S1666 Flucytosine Synonyms: Ancobon, 5-fluorocytosine, Ancotil Size Price

Flucytosine is a fluorinated pyrimidine analogue and a synthetic antimycotic drug. It is intrafungally converted 10mg O N NH2 into the cytostatic fluorouracil that undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis and disturbs the building of certain essential proteins. The 25mg HN other mechanism is the conversion into 5-flourodeoxyuridinemonophosphate which inhibits fungal DNA F 100mg synthesis. S1889 Mitoxantrone 2HCl Synonyms: NSC-310739, Novantrone Size Price H N OH O HN OH Mitoxantrone Hydrochloride is a synthetic antineoplastic anthracenedione. It is a DNA-reactive agent that 50mg HCl intercalates into DNA through hydrogen bonding, causes crosslinks and strand breaks. It also interferes with 200mg HCl RNA and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack OH O HN OH 500mg N of cell cycle phase specificity. H S1384 Mizoribine Synonyms: Bredinin Size Price

N NH2 Mizoribine is an imidazole nucleoside and an immunosuppressive agent. The immunosuppressive effect of is 10mg N due to the inhibition of DNA synthesis in the S phase of the cell cycle. Because of its relative lack of toxicity, O O 25mg OH during the past decade MZB has been frequently used instead of azathioprine as a component of HO OH immunosuppressive drug regimens. MZB is being used to treat renal transplantation patients, IgA 100mg HO nephropathy, lupus erythematosus, and nephrotic syndrome. S1915 Sulfamethoxazole Synonyms: Gantanol, Gantanol DS Size Price

O O O N Sulfamethoxazole is a sulfonamide bacteriostatic antibiotic. It is most often used as a part of synergistic 100mg S N combination with trimethoprim in a 5:1 ratio in co-trimoxazole. Sulfonamides are structural analogs and 200mg H competitive antagonists of para-aminobenzoic acid (PABA). They inhibit normal bacterial utilization of PABA H2N for the synthesis of folic acid, an important metabolite in DNA synthesis. 500mg

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CHK (Checkpoint kinase,CSK-homologous kinase)

S1532 AZD7762 Size Price

NH2 AZD7762 is a novel checkpoint kinase inhibitor with an IC50 of 5 and <10 nM for Chk1 and Chk2, respectively. 5mg O It significantly prolonged the median time required for tumor volume doubling in response to gemcitabine and NH 25mg HN radiation. G2 checkpoint abrogation and homologous recombination repair inhibition both contribute to F sensitization by Chk1 inhibition. The clinical use of AZD7762 in combination with gemcitabine and radiation for S N 200mg O H patients with locally advanced pancreatic cancer.

Dihydrofolate reductase

S1584 NSC 131463 Synonyms: NSC 133723, Deoxyaminopteroic acid, DAMPA Size Price

OH NSC 131463 is a dihydrofolate reductase potent inhibitor with an IC50 of 1 nM. It is a minor metabolite of 10mg NH O methotrexate. It inhibited L1210 cell proliferation in culture (IC50 = 0.3 μM), and prolonged the survival of 2 50mg N L1210 leukemic mice (98% increase in lifespan at 120 mg/kg, qdx9). The increased dose of mAPA-HCysA N N required to inhibit tumor growth in vitro and in vivo relative to methotrexate may reflect the inability of this 200mg compound to form non-effluxing polyglutamates. H2N N N

 Solutions to Signal Transduction Research HDAC

HDACs and histone acetyltransferases are the enzymes that determine, in part, the pattern of histone acetylation. The pattern of acetylation of histones as well as the pattern of methylation and phosphorylation of histones may represent a “code” that is recognized by non-histone complexes involved in the regulation of gene expression. There are three classes of HDAC enzymes. Class I deacetylases include HDACs 1, 2, 3, and 8, are related to yeast RPD3 deacetylase, and have molecular masses of 22–55 kDa. Class II deacetylases include HDACs 4, 5, 6, 7, 9, and 10, are related to yeast Hda1 deacetylase, and have molecular masses of 120–130 kDa. HDAC 11 contains conserved residues in the catalytic core region shared by both class I and II enzymes. The third class of HDACs are the nicotine adenine dinucleotide-dependent Sir 2 family of deacetylases, which differ from class I and II HDACs in that they are not inhibited by TSA, SAHA, or related compounds. A number of chemically diverse agents have been discovered, including the hydroxamic acids SAHA and TSA, which inhibit HDAC activity. Inhibiting HDAC activity with SAHA and related agents alters gene expression, but, contrary to what might be anticipated by the wide distribution of HDACs in chromatin, there is not a global alteration in gene transcription. Furthermore, alteration of the chromatin structure in the transcribed region of a gene has been shown to be associated with induced expression of that gene by transcription factor complexes containing RNA polymerase II.

Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. C.-Y. Gui, L. Ngo. PNAS, 2004,101(5):1241-1246

 Papers Using Selleck Products

S1030 LBH-589(Panobinostat) Induction of TAp63 by histone deacetylase inhibitors. Berna S. Sayana et al. Biochem Bioph Res Co, 2010(22):1748-1751

S1053 MS-275(Entinostat) DNMT1 Stability Is Regulated by Proteins Coordinating Deubiquitination and Acetylation-Driven Ubiquitination. Zhanwen Du, Jing Song et al. Sci Signal, 2010;146(3):ra80

Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells William Brazelle, Jenny M. Kreahling et al. PLoS One, 2010; 12(5):e14335.

S1047 Vorinostat(SAHA) A Novel Xenograft Model of Cutaneous T-cell Lymphoma. Krejsgaard T, Kopp K et al. Exp Dermatol, 2010; 19(12):1096-1102.

Itch/AIP4-independent proteasomal degradation of cFLIP induced by the histone deacetylase inhibitor SAHA sensitizes breast tumour cells to TRAIL. Rosario Yerbes et al. Invest New Drugs, 2010 Nov 25. [Epub ahead of print]

 .*') HDAC

HDAC (Histone deacetylases)

S1095 LAQ824 Synonyms: NVP-LAQ824, Dacinostat Size Price

LAQ824 is a histone deacetylase inhibitor, inhibited in vitro enzymatic activities (IC50= 0.032uM) and OH 10mg N H  |}~]" "$? )'ƒ$ Œ;œ‘<  N inhibited growth of cancer cell lines at submicromolar levels after 48-72 h of exposure, the calculated IC50s HO 50mg O "$]"$")'[__[~#Z$}ZŒ;œ‘<–€ effects in a xenograft animal model. 200mg HN Feed S1095 LAQ824 Acetyl-H3 !*[?Z;[?$"")' LAQ824 treated MDA-MB-231 breast denocarcinoma H3 cell line.

20μM 10μM 1μM 0.1μM 0.01μM 0μM Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1030 LBH-589 Synonyms: Panobinostat, NVP-LBH589 Size Price

A novel broad-spectrum HDAC inhibitor belongs to the hydroxamate class, in Philadelphia chromosome–negative 10mg (Ph-) ALL. HDACs are regulating gene transcription, protein function, and stability. The IC50 value for HN inhibition of proliferation in MOLT-4 cells is approximately 5 nM and for Reh cells is approximately 20 50mg N nM.Similar results were observed at 24 and 72 hours. H H 100mg N Feed OH S1095 LAQ824 LBH-589 17AAG 50 nM 100 nM O hours Ctr 8 8 16 24 8 16 24 Western blot analysis of Ac-tubulin and Tubulin. Cell line was treated with 50 or 100 nM LBH-589 Ac-tubulin for 8, 16, 24 hours.

Tubulin Data Provided by our customer Marianne Skeie Rødland, University of Oslo/Oslo University Hospital

S1484 MC1568 Size Price O MC1568 is a potent selective class II (IIa) histone deacetylas (HDAC II) inhibitor (IC50 of a maize deacetylase 5mg H HD2 at 22.0 μM). MC1568 had no or a weak effect on the class I HDACs. MC1568 shows no inhibitory activity N N OH against HDAC1 but was able to inhibit HDAC4. 50mg F O 100mg

S1122 MGCD0103 Synonyms: Mocetinostat Size Price

MGCD0103, an orally available small molecule, binds to and inhibits Class 1 isoforms of HDAC, specifically 5mg N [ ;~|}~]" "$])'ƒZ|}~]" "$_)'ƒ?|}~]" $##)'ƒZ€ tumor cells and so tumor cell death. In intact cells, MGCD0103 inhibited only a fraction of the total HDAC 10mg NNHN N 2 H H activity and showed long-lasting inhibitory activity even upon drug removal. MGCD0103 induced N hyperacetylation of histones, selectively induced apoptosis, and caused cell cycle blockade in various human 25mg O cancer cell lines in a dose-dependent manner.

Feed S1122 MGCD0103

Acetyl-H3 !*[?Z;[?$"")' MGCD0103 treated MDA-MB-231 breast denocarcinoma cell line. H3 H3 Produced Independently by our customer Dr.Zhang, Tianjin Medical University 20μM 10μM 1μM 0.1μM 0.01μM 0μM

S1085 Belinostat Synonyms: PXD101, PX105684 Size Price

Belinostat is a novel hydroxamate-type inhibitor of HDAC activity. Belinostat inhibits HDAC 10mg O O O activity in HeLa cell extracts with an IC50 of 27 nM. PXD101 is cytotoxic in vitro in a number of S OH 50mg N N €}~]"*"$?$<)' H H induces apoptosis. 100mg Feed S1085 Belinostat Acetyl-H3 !*[?Z;[?$"")' Belinostat treated MDA-MB-231 breast denocarcinoma H3 cell line. 20μM 10μM 1μM 0.1μM 0.01μM 0μM Produced Independently by our customer Dr.Zhang, Tianjin Medical University

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 HDAC .*')

S1422 Droxinstat Size Price

O Droxinostat is a selective inhibitor of HDAC3, HDAC6, and 6and8. Droxinostat shows comparable inhibition of 5mg O OH [ ;~#[ ;~‘|}~]" $<$<#)ŒZƒ€*[ ;~?|}~]" #$_ N 10mg H )Œƒ$*€€ development and progression. This agent could sensitize malignant cells to death receptor ligands (Fas and Cl 25mg TRAIL). Feed S1422 Droxinstat Acetyl-H3 Western blot analysis of H3, Acetyl-H3. 0.01-10 )' Droxinstat treated MDA-MB-231 breast denocarcinoma H3

cell line. ")'

"$)' Control )' "$")' Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S2170 ITF2357 Synonyms: Givinostat, Gavinostat Size Price

H N+ ITF2357 is a HDAC inhibitor of the hydroxamate family, which inhibits both class I and class II HDAC. ITF2357 10mg H O N induces apoptosis of MM and AML cells and this apoptosis takes place following induction of p21 and H down-modulation of Bcl-2 and Mcl-1 proteins. When tested on normal cells, ITF2357 inhibits the production of 25mg Cl- O N OH *€}ŒZ}Œ#Z\Z}\€* O 50mg H2O IL-6 and VEGF by mesenchymal stromal cells.

S1096 JNJ-26481585 Size Price

JNJ-26481585 is an orally bioavailable, hydroxamic acid-based inhibitor of HDAC with potential antineoplastic 10mg N H activity. HDAC inhibitor JNJ-26481585 inhibits HDAC leading to an accumulation of highly acetylated histones, N N N H which may result in an induction of chromatin remodeling; inhibition of the transcription of tumor suppressor 50mg N N OH genes; inhibition of tumor cell division; and the induction of tumor cell apoptosis. O 200mg Feed S1096 JNJ-26481585 Acetyl-H3 Western blot analysis of H3, Acetyl-H3. 0-20 )'

H3 JNJ-26481585 treated MDA-MB-231 breast denocarcinoma cell line.

JNJ-26481585(­M) 0 0.01 0. 1 1.0 10.0 20.0 Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1053 MS-275 Synonyms: Entinostat, SNDX-275, MS-27-275 Size Price

O MS-275 is synthetic benzamide derivative with potential antineoplastic activity. This agent preferentially 5mg N inhibits HDAC1 (IC50=300 nM) over HDAC3 (IC50=8 μM) and has no inhibitory activity towards HDAC8 NH H (IC50>100 μM). This agent appears to exert dose-dependent effects in human leukemia cells at low drug 10mg O N NH2 concentrations in human prostate cancer cell lines. 25mg O Feed S1053 MS-275 Acetyl-H3 !*[?Z;[?$"")' MS-275 treated MDA-MB-231 breast denocarcinoma H3 cell line.

20μM 10μM 1μM 0.1μM 0.01μM 0μM Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1090 PCI-24781 Synonyms: CRA-02478 Size Price

O OH NH PCI-24781 is a novel broad spectrum hydroxamic acid-based inhibitor of HDAC that shows antitumor activity 10mg O O in vitro and in vivo and is under evaluation in phase I clinical trials. PCI-24781 inhibited pure recombinant HN HDAC1 with a Ki of 0.007 Mmol/L, and also inhibited the other HDAC isozymes HDAC2, HDAC3/SMRT, 50mg O HDAC6, HDAC8, and HDAC10 in the nanomolar range. N 200mg

S2190 Pyroxamide Synonyms: NSC 696085, NSC-696085 Size Price O H Pyroxamide is a potent HDAC inhibitor with an IC50 of 100 nM for HDAC-1. Despite the potent 10mg N OH N growth-inhibitory effects of pyroxamide in this CWR22 prostate cancer xenografts model, serum H prostate-specific antigen levels in control versus pyroxamide-treated mice were not significantly different. It 50mg O causes the accumulation of acetylated core histones in MEL cells cultured with the agent. N 200mg

 Solutions to Signal Transduction Research .*')9OXROQK,GSOR_*KGIKZ_RGYK HDAC

S1515 SB939 Size Price

O SB939 is a novel potent and orally active HDAC inhibitor with an IC50 of 52 nM for HDAC1 and a GI50 of 0.56 10mg HO N μM for Colo205. Its IC50 for HCT-116 colon cancer cell line and HL-60 acute myeloid leukemia cell line is 0.48 N 50mg H )'"'Z$}Z^_?_}Z}}Z}†[ ;~Z**• N binding enzymes, and shows significant antiproliferative activity against a wide variety of tumor cell lines. 200mg Feed S1515 SB939 N Acetyl-H3 !*[?Z;[?$"")' SB939 treated MDA-MB-231 breast denocarcinoma H3 cell line.

Produced Independently by our customer Dr.Zhang, Tianjin Medical University ")'

"$)' Control )' "$")'

S1168 Sodium valproate Synonyms: valproate Sodium, Depakene, Valproate, Valrelease Size Price O Sodium valproate is a HDAC inhibitor with an IC50 of 0.4 mM and exhibits anticancer, anti-inflammatory and 10mg ONa neuroprotective effects. Sodium valproate can inhibit cell apoptosis. It displays anticonvulsive activity via an 50mg ;^;  ; €$ } € \' ; –Z  voltage-gated Na+ channels and modulates firing of neurons. It enables induction of pluripotent stem cells from 200mg somatic cells by Oct4 and Sox2.

S1045 Trichostatin A Synonyms: TSA Size Price

Trichostain A is an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture. 1mg TSA inhibited proliferation of eight breast carcinoma cell lines with mean ± SD IC50 of 124.4 ± 120.4 nm. O O HDAC inhibitory activity of TSA was similar in all cell lines with mean ± SD IC50 of 2.4 ± 0.5 nm, and TSA 10mg OH N treatment resulted in pronouncing histone H4 hyperacetylation. H 50mg N Feed S1045 Trichostatin A Acetyl-H3 !*[?Z;[?$"")' Trichostatin A treated MDA-MB-231 breast denocarcinoma cell line.

Produced Independently by our customer Dr.Zhang, Tianjin Medical University H3 20μM 10μM 1μM 0.1μM 0.01μM 0μM

S1047 Vorinostat Synonyms: Zolinza, MK-0683, SAHA Size Price

†**€';|?)'ƒ*<€$ 100mg O Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after H <‘ € * Z $ ~ * * '; ? )' 500mg N OH N vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. H 1g O

Feed S1047 Vorinostat

SAHA promotes C2C12 †€$\š W~} ^ƒWƒ¬ differentiationIn the images, the s.c. with 1 · 106 MyLa2059 cells into both flanks.When the mice had developed red is the myotube indicating established palpable tumors treatment was initiated (day 1). The mice received differentiation, |ƒ#"W|ƒ$$*$ the blue is the nuclei. In total, there were four mice in the group receiving vehicle and three mice in Data from Experimental thegroup receiving vorinostat. The length and width of the tumors were measured control SAHA 31nm Dermatology 2010 using our continuously until the experiment was terminated on day 20 post treatment initiation. product.

S1194 CUDC-101 Page 4

Sir2-like Family Deacetylase

S1541 EX 527 Synonyms: SEN0014196 Size Price

O EX 527 is a potent and selective SIRT1 class III HDAC enzyme inhibitor with an IC50 of 38 nM. It is Selective 100mg inhibitor of SIRT1 that does not class I/II inhibit HDAC or other sirtuin deacetylase family members (SIRT1, H2N H N SIRT2, SIRT3, HDAC and NADase respectively). It was thought to block the release of deacetylated peptide 500mg and O-acetyl-ADP-ribose from the enzyme following the deacetylation process. Blocking of SIRT1 by EX 527

also demonstrated that deacetylation of the important tumor suppressor protein p53 is mediated by SIRT1 as 1g well. Cl

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Apoptosis

Apoptosis is a genetically controlled and evolutionarily conserved form of cell death that is of importance for normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. Apoptotic cell death is triggered by extrinsic, receptor-mediated, or intrinsic, mitochondria- mediated, signalling pathways that induce death-associated proteolytic and/or nucleolytic activities.

All pathways to apoptosis converge on the activation of caspases, which are cysteinyl aspartate proteases that coordinate the efficient dismantling and engulfment of doomed cells. Two pathways of cell death can be distinguished by whether they require BCL-2 family proteins and by which caspases are crucial for their execution. Survivin is a member of the inhibitor of apoptosis gene family. Although survivin-like IAP molecules in model organisms seem to participate cytoki- nesis, reduction or loss of survivin in mammalian cells has been associated with panoply of cell division defects that include supernumerary centrosomes, aberrant spindle assembly, mislocalization of mitotic kinases, loss of mitotic checkpoint(s), and cytokinesis failure with appearance of multinucleated cells.

p53 can induce apoptosis through its well defined role as a regulator of transcription, but also by a less well defined transcription independent mechanism. p53 mediates mitochondrial permeabilization through direct physical interactions with the pro-apoptotic Bcl-2 family members, Bax and Bak.

Regulation of Cell Death: The Calcium-Apoptosis Link. Sten Orrenius et al. Nat Rev Mol Cell Bio, 2003(4):552-565 The BCL-2 protein family: opposing activities that mediate cell death. Richard J. Youle et al. Nat Rev Mol Cell Bio, 2008(9):47-59 Fatal liaisons of p53 with Bax and Bak. Jean-Luc Perfettini et al. Nat Cell Bio, 2004;6(5):386-388. Survivin Modulates Microtubule Dynamics and Nucleation throughout the Cell Cycle. Jack Rosa et al. MBoC, 2006(17):1483-1493.

 Papers Using Selleck Products

S1001 ABT-263(Navitoclax) Diminished sensitivity of Chronic Lymphocytic Leukemia cells to ABT-737 and ABT-263 due to albumin binding in blood. Meike Vogler et al. Clin Cancer Res, 2010(16):4217

S1002 ABT-737 Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. Sarah R. Walmsley et al. J Clin Invest, 2011; 121(3):1053-1063

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid. Antonello A. Romani et al. Cancer Chemother Pharmacol, 2011;67(3):557-567

ABT-737 Overcomes Resistance to Immunotoxin-Mediated Apoptosis and Enhances the Delivery of Pseudomonas Exotoxin–Based Proteins to the Cell Cytosol. Roberta Traini et al. Mol Cancer Ther, 2010; 9(7):2007-2015

%?€€$ Emma Y. Song et al. Exp Hematol, 2010; 38(10):908-921.e1

]? Ÿ€ '€ *; |„Ÿ';ƒ; ~€ „ ~ Apoptosis Induced by Proinflammatory Cytokines and Endoplasmic Reticulum Stress. Esteban N. Gurzov et al. J Bio Chem, 2010; 285(26):19910-19920

Histone deacetylase inhibitors synergistically potentiate death receptor 4-mediated apoptotic cell death of human T-cell acute lymphoblastic leukemia cells. Eun-Sil Sung et al. Apoptosis, 2010; 15(10):1256-1269

 Apoptosis (IR

Bcl-2 (B-cell lymphoma 2)

S1001 ABT-263 Synonyms: Navitoclax Size Price

O O O The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation.A 5mg S SPh N wide range of SCLC cellular activity was observed with ABT-263 having aEC50 of 110 nmol/L against the most H |[<#ƒZ|[‘ƒ€~]")Œ$} 10mg N N N O H N S O ~]"®)Œ$ F C O 3 25mg 100 ABT-263 (EC50 64.9 nM) Feed S1001 ABT-263

80 CLL cells freshly isolated from peripheral blood of CLL patients Cl were incubated in RPMI + 10% FCS with different concentrations 60

cells of ABT-737 or ABT-263 for 4 h before apoptosis was assessed by + 40 externalization of phosphatidylserine (PS) and staining with

% PS AnnexinV-FITC (n=21, *=P<0.05). 20 Data from AACR. July 2 2010 using our product. 0 0 1 3 10 30 100 300 1000 (nM) S1002 ABT-737 Size Price

NO 2 H N S H ABT-737 is a pan-Bcl-2 inhibitor that has a wide range of single-agent activity against ALL cell lines and 5mg O N S O O N xenografts. Increased expression of the Bcl-2 family of proteins in cancers has been associated with chemotherapy resistance. The ABT-737 single-agent LC90 values ranged from 100 nM for COG-LL-319 and 10mg N RS4;11 cells to low micromolar concentrations for the other ALL cell lines. N 50mg

Cells were exposed to ABT-737 at a concentration Cl Feed ranging from 1 to 50 lM. Following 72 h of incubation, S1002 ABT-737 growth inhibition was analyzed by crystal violet assay. Dose–effect plot of ABT-737 treatment is presented. ' ^';?–?")' Lower panel detection of PARP-1, cleaved caspase-9 cisplatin in the absence or in the presence and caspase-3, BCL-2 and MCL-1 in TFK-1 and EGI-1 of 100nM ABT737. The cell were stained cells after 72 h of ABT-737 treatment (1, 3, 10, 25,50 with Hoechst 33342 , MitoTracker Red lM). Cell lysates were analyzed on Western blotting. and yo-pro-1. Data Provided by our customer Prof. Angelo F, Borghetti Produced Independently by our customer of Universita degli Studi di Parma Dr.Zhang, Tianjin Medical University.

S1057 Obatoclax Mesylate Synonyms: GX15-070 Size Price

Specific apoptosis was induced at 250 nM obatoclax (16.04 %) and increased in a dose-dependent manner 5mg HN up to the highest dose tested (10 μM, 73.48 %). The average IC50 for the seven AML patient samples tested CH3SO3H was 3.59 μM. Obatoclax has been reported to similarly antagonize all antiapoptotic Bcl-2 family proteins 10mg N (average IC50=3 μM), including Mcl-1 (IC50=2.9 μM) and Bfl-1 (IC50=5 μM). 25mg N Feed H O S1057 Obatoclax Mesylate ' ^';?–?")' MEF cells were treated for 24 hrs with the Bcl-2 cisplatin in the absence or in the presence antagonists Obatoclax mesylate at the indicated of 100nM Obatoclax Mesylate. The cell were doses. Acute survival was monitored by propidium stained with Hoechst 33342 , MitoTracker iodide uptake assays (red lines). Long term survival Red and yo-pro-1. (red lines) was measured by replacing the drug-containing media with normal media and Produced Independently by our customer Dr.Zhang,Tianjin Medical University. incubating the cells until visible colonies formed. Clonogenic survival is expressed relative to the numbers of colonies formed following 24 hr incubation in normal media (lacking drugs).

Data provided by our customer Dr Christine Hawkins, c/o Biochemistry Department Office，La Trobe University S1121 TW-37 Size Price

TW-37 binds to the BH3 binding groove in Bcl-2 protein competing with BH3 peptides derived from Bid, Bim, 10mg O and Bad proteins. TW-37 binds to Bcl-2 with a K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high O 20mg S affinities. TW-37 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and O effectively induces apoptosis in a dose-dependent manner. 200mg N H Feed S1123 TW-37 HO OH OH MEF cells were treated for 24 hrs with the Bcl-2 antagonists TW-37 at the indicated doses. Acute survival was monitored by propidium iodide uptake assays (red lines). Long term survival (red lines) was measured by replacing the drug-containing media with normal media and incubating the cells until visible colonies formed. Clonogenic survival is expressed relative to the numbers of colonies formed following 24 hr incubation in normal media (lacking drugs). Data provided by our customer Dr Christine Hawkins,c/o Biochemistry Department Office， La Trobe University

 Solutions to Signal Transduction Research :4,śV9[X\O\OT Apoptosis

S1029 Lenalidomide Synonyms: CC-5013, Revlimid Size Price

10mg O Œ*|}~]" ") M). It was initially intended as a treatment for multiple myeloma. Lenalidomide inhibits TNF-alpha production, 50mg stimulates T cells, reduces serum levels of the cytokines VEGF and bFGF, and inhibits angiogenesis. This N O agent also promotes G1 cell cycle arrest and apoptosis of malignant cells. 200mg NH Feed A B S1029 Lenalidomide O '';_‘?|"$])'ƒZ|)'ƒ NH2 combined therapy for 72 hours. Annexin/PI staining show increased apoptosis associated with caspase 8 and PARP cleavage after 18 and 36 hours of exposure. B) MM.1S cells were treated with AT9283 |"$])'ƒZ|)'ƒ*<€$ Whole lysates were immunoblotted with indicated antibodies Data from our customer DANA-FARBER CANCER INSTITUTE using our product.

S1567 Pomalidomide Synonyms: CC-4047, Actimid Size Price

NH2 O „\€€}~]"*)'$}€R 10mg necessary blood vessel growth. Compared to thalidomide, pomalidomide has demonstrated enhanced N O immunological effects in lab testing, including an approximately 500-2,000 times greater potency at stimulating 50mg NH the proliferation of T-cells. Pomalidomide appears to function through multiple pathways to inhibit myeloma O O R€$ 200mg p53 (protein 53)

S1172 JNJ 26854165 Synonyms: Serdemetan Size Price

JNJ-26854165 is an orally bioavailable, small-molecule HDM2 antagonist with potential antineoplastic activity. 5mg H N This agent inhibits the binding of the HDM2–p53 complex to the proteasome, blocking the degradation of p53. NH In addition to p53, degradation of other HDM2 client proteins may be inhibited. HDM2, a zinc finger protein, is 25mg HN a negative regulator of the p53 pathway; often overexpressed in cancer cells, this oncoprotein has been implicated in cancer cell proliferation and survival. 100mg N Survivin

S1130 YM155 Size Price

N YM155, a novel small molecule survivin inhibitor, suppressed expression of survivin and induced apoptosis in 10mg O PC-3 and PPC-1 human HRPC cell lines at 10nmol/L. Pharmacokinetic analyses indicated that YM155 is N highly distributed to tumors and at concentrations f20-fold higher than those in plasma. 50mg N Br Feed S1130 YM155   200mg N  4GIR Total RNA from livers of these mice were isolated from tissues O using TRIZOL (Invitrogen). cDNA synthesis was performed with   the M-MLV RTase cDNA Synthesis Kit.qRT-PCR reactions were O  4GIR   performed using SYBR Greenon ABI 7500 Fast system. Expression ?3 levels of Survivin gene were measured by qRT-PCR in livers injected with 0.9% NaCl or YM155 48 hours after DEN treatment.

Data from our customer Lihua Min , Chinese Academy of Sciences

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 PARP

The members in the PARP superfamily related to the activity of DNA mainly include PARP1, PARP2, Tank1, and Tank2. PARP1 accounts for at least 80% of total cellular PARP activity, and together with its nearest relative PARP2, constitutes the DNA-damage-dependent PARPs. PARP1 poly(ADP- ribosyl)ates various nuclear proteins including histones H1 and H2B, XRCC1, CENP-A, CENP-B, BUB3, and itself, whereas PARP2 adds PAR to XRCC1, CENP-A, CENP-B, BUB3, and itself. Most of those proteins are involved in the activities of DNA and centrosomes, especially in DNA-damage repair, specifically the base excision repair. Once one strand of DNA breaks, PARP1/2 bind to the nicked site, which activates their own enzymatic activity, causing the poly(ADP-ribosyl)ation of PARP1/2 and other nuclear proteins including histones and XRCC1 at the expense of NAD+. Consequently, \;}}}°‚~~–€ poly(ADPribosyl) ated PARP1/2 to repair the SSB.

Since 2005, the rapid development of PARP inhibitors for cancer therapy has brought at least 7 PARP inhibitors into clinical anticancer investigations, and 2 of them have entered phase III clinical trials for cancer therapy. The encouraging results from those clinical studies further reveal a promising future of targeting PARP as an anticancer strategy.

Poly(ADP-ribose) polymerase inhibitors as promising cancer therapeutics. Jin-xue He et al. Acta Pharmacol Sin, 2010(31):1172–1180.

 Papers Using Selleck Products

S1004 ABT-888(Veliparib) ABC transporters in the blood-brain barrier limit the brain penetration of the PARP inhibitor ABT-888 Lin Fan et al. AACR 2010.

S1098 AG-014699(PF-01367338) Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability. Daniel Corta´zar et al. Nature, 2011(470):419–423

S1060 AZD2281(Olaparib) MSH3 Mediates Sensitization of Colorectal Cancer Cells to Cisplatin, Oxaliplatin, and a Poly(ADP-ribose) Polymerase Inhibitor. Masanobu Takahashi et al. J Bio Chem, 2011(286):12157-12165

S1087 BSI-201 Tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 mediate cerebral ischemia-induced poly(ADP-ribose) polymerase-1 activation and neuro- nal death. Haile WB et al. Neuroscience, 2010; 171(4):1256-1264.

 PARP 6'86

PARP (Poly (ADP-ribose) polymerase)

S1004 ABT-888 Synonyms: Veliparib Size Price

H2N O ABT-888 is a potent inhibitor of both PARP-1 and PARP-2 by [3H]NAD+ with Kis of 5.2 and 2.9 nmol/L, 5mg respectively. The compound has good oral bioavailability and crosses the blood-brain barrier. ABT-888 N strongly potentiated temozolomide in the B16F10 s.c. murine melanoma model. In the MX-1 breast xenograft 10mg model, ABT-888 potentiated cisplatin, carboplatin, and cyclophosphamide, causing regression of established N N tumors, whereas with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited. 25mg H H -XRCC1 -PAR DAPI/DNA * ***control Feed S1004 ABT-888 451 Lu cells, 120 h treatment

no 120 Fluorometric analysis result of Caption: 451 Lu is a melanoma cell line with high PARP 100 Vehicle 80 1 nM „;‚$")';^‘‘‘ expression that is resistant to temozolomide. Treatment was added. with 25 μM ABT-888 greatly increased sensitivity to 60 40 10 nM 25 μM temozolomide compared to cells without ABT-888 20 ABT-888 % relative viable cells treatment as measured by MTS assay. 0 100 nM Data from our customer Dr David 0 50 100 150 200 250 300 350 400 Schürmann, University of Basel， Data from our customer Dr Steve Reuland,UC Denver, [Temozolomide, μM] 1 μM switzerland AMC,usa

S1098 AG-014699 Synonyms: AG-14447, AG-014447, AG-14699, PF-01367338 Size Price

F AG-014699 is a PARP inhibitor (Ki, 1.4 nmol/L) with outstanding in vivo chemosensitization potency, which is 5mg HO greater chemosensitization of temozolomide at a dose of 1 mg/kg. AG-014699 is a tricyclic indole PARP NH OH O P inhibitor with potential antineoplastic activity. It blocks base excision repair mediated by PARP 1 on single 10mg O H OH strand breaks and may be particularly efficacious in inducing apoptosis in breast cancer associated gene-1 N HN and -2 (BRCA1/2) deficient tumor cells. 50mg

-XRCC1 -PAR DAPI/DNA * ** *control Feed S1098 AG-014699

no

€€*„;‚$")';"<#__ 1 nM was added.

10 nM Data from our customer Dr David Schürmann，University of Basel，switzerland

100 nM

1μ M

S2178 AG14361 Size Price

N AG14361 is a potent PARP-1 inhibitor with a GI50 of 10.9 μM. It caused a >3-fold sensitization of PARP-1+/+ 10mg ®$<*•„;‚„%%$}]#Z;

1(: F A-966492 is a highly potent and efficacious PARP inhibitor with a Ki and EC50 of 1 nM. In addition, it is orally 10mg N bioavailable across multiple species, crosses the blood-brain barrier, and appears to distribute into tumor 50mg N N tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in H H combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in H2N O combination with carboplatin. 200mg

S1060 AZD2281 Synonyms: Olaparib, KU-0059436, KU0059436 Size Price

O PARP is anenzyme that is involved in a specific kind of DNA repair called base-excision repair, which is used 5mg N * \;$}~]"*;› ‘|)'ƒŠ„;‚„ "$""]Z„;‚„ "$""Z N NH PF50=25.8. AZD2281(Olaparib) at 400 mg twice daily is well tolerated and highly active. The toxicity that was 25mg O N seen in BRCA1/BRCA2 carriers was similar to the previously reported toxicity in noncarriers. F O Feed S1060 AZD2281 100mg

Effect of AZD 2281 on the viability of endometrial cancer cell line Hec50 and Ishikawa and ovarian cancer cell line SKOV3,Caov3 and PA-1 was detected by WST-1 method after 3 days treatment. Data from our customer Dr Meng Xiangbing, The University of Iowa.

 Solutions to Signal Transduction Research 6'86 PARP

S1087 BSI-201 Synonyms: Iniparib, NSC-746045, IND-71677 Size Price

BSI-201 is a small molecule believed to achieve its anti-neoplastic effect by covalently binding and inhibiting 10mg H2N O PARP-1. BSI-201 is active against a broad range of cancer cells in culture, including drug resistant cell lines. BSI-201 has shown a strong safety profile and no significant toxicities attributable to drug in studies of more 50mg than 200 patients treated to date with monotherapy, as well as in combination with chemotherapeutic regimens. 200mg Feed S1087 BSI-201

The interaction between TWEAK and Fn14 induces PARP-1 cleavage and NO2 accumulation of Poly(ADP-ribose) polymers in vitro and in vivo.(A–C) Representative Western blot analysis and quantification of the mean intensity of the band of total PARP-1(E) and caspase 3 activation (F) in Wt neurons I incubated with TWEAK either alone or in combination with the PARP-1 inhibitor BSI-201. * P<0.05 compared to cells co-treated with BSI-201.

Data from Neuroscience 171 (2010) 1256–1264 using our product.

S1132 INO-1001 Size Price

NH2 INO-1001 is an isoindolinone derivative and potent inhibitor of the nuclear enzyme PARP with 10mg chemosensitization and radiosensitization properties. INO-1001 inhibits PARP, which may result in inhibition of tumor cell DNA repair mechanisms and, so, tumor cell resistance to chemotherapy and radiation therapy. 25mg O INO-1001 improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and reduces pulmonary injury associated. 50mg NH2

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Aurora Kinase/ksp

The Aurora kinase family is a collection of serine/threonine kinases that functions as key regulators of cell division. Three Aurora kinases (known as Aurora A, Aurora B and Aurora C) are expressed in mammalian cells, each carrying out a distinct biological function. Aurora A localizes to spindle poles and has a crucial role in bipolar spindle formation. Aurora B, a chromosome passenger protein, localizes to centromeres in early mitosis and then the spindle midzone in anaphase, and is required for mitotic histone H3 phosphory- lation, chromosome biorientation, the spindle assembly checkpoint and cytokinesis. Aurora C is also a chromosomal passenger protein and, in normal cells, its expression is restricted to the testis where it functions primarily in male gametogenesis. As the Aurora kinases serve essential functions in mitosis, considerable attention has been given to targeting this family of kinases for cancer therapy. Several small-molecule inhibitors have been developed including Hesperadin, ZM447439, VX-680/MK0457, AZD1152 and MLN8054.

Kinesin spindle protein (KSP) provides the propulsive forces required to separate centrosomes during prophase, enabling them to migrate to opposite poles and establish a functional bipolar spindle. Ksp is greatly expressed in proliferating over non-proliferating cells and in tumour tissue relative to normal tissue. In in vitro experiments, cells treated with the prototype KSP inhibitor, monastrol, displayed abnormal, monopolar spindles with chromosomes attached via microtubules to a single pole, resulting in deranged cell division, mitotic cell cycle arrest and apoptosis.

Identification of genes that confer tumor cell resistance to the Aurora B kinase inhibitor, AZD1152. J Guo et al. Pharmacogenomics J, 2009(9): 90–102. A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours. S P Blagden, L R Molife et al. Br J Canc, 2008(98):894–899.

 Papers Using Selleck Products

S1147 AZD1152-HQPA(Barasertib) System-Level Analysis of Neuroblastoma Tumor–Initiating Cells Implicates AURKB as a Novel Drug Target for Neuroblastoma. Olena Morozova et al. Clin Cancer Res, 2010(16):4572

S1133 MLN8237 Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237. Dominic A. Sloane et al. ACS Chem Biol, 2010; 5(6):563–576

Emerging drugs for high-grade osteosarcoma. Hattinger CM et al. Expert Opin Emerg Drugs, 2010;15(4):615-34

Uncovering new substrates for Aurora A kinase. Teresa Sardon et al. EMBO reports, 2010(11):977-984

S1048 VX-680(Tozasertib) Activity of the Aurora Kinase Inhibitor VX-680 against Bcr/Abl-Positive Acute Lymphoblastic Leukemias. Fei F et al. Mol Cancer Ther, 2010;9(5):1318-1327

 Aurora/Ksp '[XUXG1OTGYK

Aurora Kinases

S1451 Aurora A Inhibitor ĉ Size Price

N N Aurora A Inhibitor ĉ;€;|;€;Š}~]""$""?<)'“;€^Š}~]"?$<)'ƒZ 10mg

O Cl (B / A ratio=1000). Aurora A Inhibitor I belongs a class of 2,4-dianilinopyrimidine inhibitors. Its selectivity for NH O Aurora A is 1000 folds over Aurora B, both in enzymatic assays and in cellular phenotypic assays. Thr217 of 50mg NN N H Aurora A is the critical residue as a “gating” binding to this agent, which is responsible for the enhanced N 200mg H selectivity over Aurora B. F S1147 AZD1152-HQPA Synonyms: Barasertib Size Price

AZD1152 is a dihydrogen phosphate prodrug of a pyrazoloquinazoline Aurora kinase inhibitor and is converted N O N 5mg HO rapidly to the active AZD1152-HQPA in plasma. AZD1152-HQPA is a highly potent and selective inhibitor of N Aurora B (Ki, 0.36 nM) compared with Aurora A (Ki, 1,369 nM) and has a high specificity versus a panel of 50 HN 10mg other kinases. Consistent with inhibition of Aurora B kinase, addition of AZD1152-HQPA to tumor cells in vitro HN N NH O induces chromosome misalignment, prevents cell division, and consequently reduces cell viability and induces 50mg F apoptosis. Feed S1147 AZD1152-HQPA

Neuroblastoma TICs are sensitive to Aurora B kinase inhibition. A. Western 6 blot analysis confirmed the presence of AURKB protein in NB TICs but not SKPs. B&C.7 shRNA knockdown of AURKB reduces the proliferation of NB TICs. Growth curves of 8 NB TICs infected with shRNA against AURKB or controls are shown in B, qRT PCR 9 was used to determine the effectiveness of AURKB knockdown (76-86%) D. The 10 alamarBlue assay revealed that AURKB inhibition with AZD1152 was effective in NB 11 }~~]"*$]<$#)'Z;Ÿ‚^**„$<)'$

Data from Clinical Cancer Research. July 22, 2010 using our product.

S1519 CCT129202 Size Price

O N

N S ~~_";€}~]"*"$"</"$"Z"$_‘/"$"]Z"$/"$"#<)Œ 10mg H N for Aurora A, Aurora B, and Aurora C, respectively. It showed high selectivity for the Aurora kinases over a N panel of other kinases tested and inhibits proliferation. The results showed that the CCT129202 is an 50mg Cl N N ATP-competitive inhibitor of recombinant Aurora A kinase with a Ki of 49.8 nmol/L. N N 200mg H S1103 ZM-447439 Size Price

N ZM447439 dose-dependently inhibited proliferation of all three cell lines (BON, QGP-1 and MIP-101) with IC50 N 10mg O values in the nanomolar to low micromolar range. Moreover, aurora kinase inhibition by ZM447439 potently NH induced apoptosis, which was accompanied by DNA fragmentation and caspase 3 and 7 activation. 25mg ON O ZM447439 Feed S1103 ZM-447439 50mg Aurora A HN Western blot analysis of Aurora A, p-Aurora A/B/C, Histone H3 and p-Histone H3. "")'›'<<

P-Histone H3 10 0.01 0.1 Control 0.001 1

M )

M )

M )

M )

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S1181 ENMD-2076 Size Price

N NH ENMD-2076 is an Aurora A/angiogenic kinase inhibitor with potent activity against Aurora A and multiple 10mg HN tyrosine kinases linked to cancer and inflammatory diseases. ENMD-2076 is relatively selective for the Aurora N A isoform in comparison to Aurora B. ENMD-2076 has demonstrated significant, dose-dependent preclinical 50mg N N activity as a single agent, including tumor regression, in multiple xenograft models. N 200mg

Feed S1181 ENMD-2076 ENMD-2076 has been tested it on two different neuroblastoma Histone H3 cell lines (SK-N-BE(2) and CHP-134) ，being calculated the IC50 Western blot analysis of Aurora A, p-Aurora A/B/C, by a WST-1 (Roche) proliferation assay, as shown in the table below. p-Histone H3 [[?[[?$"")'\' "# Its in vitro activity is in the micromolar range and has a comparable was added. effect on both lines. VX-680 was used as standard, and it proved more IC50(μM) SK-N-BE(2) CHP-134 Aurora A Produced Independently by our customer Dr.Zhang, potent on CHP-134 cells. Tianjin Medical University Data from our customer Antonino Maria Spartà, ENMD-2076 4.48 6.64 p-Aurora vx-680 7.01 0.9 A/B/C Centre for Integrative Biology (CIBIO) University of Trento 0μM 0.001μM 0.01μM 0.1μM 1μM 10μM

 Solutions to Signal Transduction Research '[XUXG1OTGYK Aurora/Ksp

S1529 Hesperadin Size Price

N Hesperadin is a human Aurora B inhibitor with an IC50 of 40 nM for the prevention of the phosphorylation of 10mg substrate. Growth of cultured bloodstream forms was also sensitive to Hesperadin with an IC50 of 50 nM. It blocked nuclear division and cytokinesis, but not other aspects of the cell cycle. Hesperadin also causes cells 50mg NH O H N arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3-5 S O O N h. H 200mg S1100 MLN8054 Size Price

O OH MLN8054 is an orally bioavailable, highly selective small molecule inhibitor of the Aurora A kinase with 10mg HN potential antineoplastic activity. MLN8054 inhibits recombinant Aurora A kinase activity in vitro and is selective N N *;€;|}~]" "$""<)'ƒ*;€^|}~]" "$)'ƒ€€$'Œ\‘"]< 50mg

Cl N treatment results in G2/M accumulation and spindle defects and inhibits proliferation in cultured human tumor F F |}~]""$"$‘#)'ƒ$ 200mg

S1133 MLN8237 Size Price

OH MLN8237 is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the Aurora A 5mg HN kinase. MLN8237 binds to and inhibits After treatment in eight multiple myeloma cell lines with MLN8237 Cl N O |"$""")'M<)'ƒ*<‘Z***;€;***|"$")'ƒ 10mg N O was examined. Tumor burden was significantly reduced and overall survival was significantly increased in O animals treated with 30mg/kg MLN8237. 50mg N Feed S1133 MLN8237 F Inhibition of Aurora A (12.5 nM) by MLN8054 or MLN8237 was assessed in €""³'´?„³;„¶€* by p81 phosphocellulose assay and scintillation counting. Kinase activity is reported as a percentage of control calculated from duplicate incubations containing 2.5% (v/v)DMSO.

Data from ACS Chem. Biol., 2010, 5 (6) using our product.

S1454 PHA-680632 Size Price

O N N N NH PHA-680632 is the first representative of a new class of Aurora inhibitors (Aurora A/B/C IC50 at 27, 135 and 10mg HN 120 nM, respectively). PHA-680632 is active on a wide range of cancer cell lines and shows significant tumor N 50mg O growth inhibition in different animal tumor models at well-tolerated doses. The IC50 of PHA-680632 for cell HN anti-proliferation ranged from 0.11 μM to 5.6 μM. 200mg

S1154 SNS-314 Mesylate Size Price

N SNS-314 Mesylate is an ATP-competitive, potent and selective inhibitor of Aurora kinases A (IC50=9.0nM), B 10mg NH Cl (IC50=31nM), and C (IC50=3.4nM). Histone H3 phosphorylation was potently inhibited by SNS-314 in all 6 cell S HN NH lines. SNS-314 Mesylate represents a new class of highly potent Aurora kinase inhibitors and is being O 50mg S N evaluated in a phase-1 dose escalation study designed to assess safety and tolerability in patients with advanced solid malignancies. 200mg N O S OH Histone H3 Feed S1154 SNS-314 Mesylate O p-Histone H3 Western blot analysis of Aurora A, p-Aurora A/B/C, Aurora A [[?[[?$"")'\?<' was added. p-Aurora A/B/C 0μM 0.001μM 0.01μM 0.1μM 1μM 10μM Produced Independently by our customer Dr.Zhang, SNS-314 Tianjin Medical University

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Aurora/Ksp '[XUXG1OTGYK1YV

S1048 VX-680 Synonyms: MK-0457, Tozasertib Size Price

H N N S VX-680 is the inhibitor of Aurora-A,-B,-C kinases with apparent inhibition constant values of 0.6,18,4.6 nM 25mg N N respectively.VX-680 caused accumulation of cells with 4N DNA content and potently inhibited the proliferation N NH H of a wide variety of tumor cell types with IC50 values ranging from 15 to 113 nM.VX-680 had no effect on the N 100mg O viability of noncycling primary human cells at concentrations as high as 10uM. N 300mg

VX-680 and dasatinib synergize to induce cytotoxic activity in wild-type Bcr/Abl-positive human ALL cells. A, TXL2 and UCSF02 cells were exposed )Œ†°#‘"€""Œ*<€Z** blue exclusion. B, TXL2 cells were treated with or without VX-680 and dasatinib for 48 hours in triplicate. **, P < 0.001, VX-680 and dasatinib cotreated TXL2 compared with VX-680–treated or dasatinib alone–treated TXL2 cells. Apoptotic cells were defined by flow cytometry as Annexin V and propidium iodide (PI) double-positive cells. C, TXL2 cells were exposed to VX-680 and/or dasatinib and cell cycle distribution was assessed by flow cytometry.

Data published in Mol Cancer Thel;9(5) 1318-1327 using our product.

Feed S1048 VX-680

‚*€;ŒŒ†°#‘"$;Z^Œœ)Œ†°#‘"*?$;*?Z€ removed from the medium and cells were cultured without VX-680. During this period (days 3–21) without drug, viability (top left), cell numbers (bottom left), and cell cycle distribution (right) of BLQ1 cells were assessed. B, BLQ1 and BLQ1-VX-Tx cells were cytospun onto glass slides and fixed, dried, and stained !$;&#?*$~Z^Œœ^Œœ†°–$])Œ†°#‘"]Œ for 72 hours. Cell viability was measured by trypan blue exclusion. *, P < 0.05, vincristine-treated BLQ1 compared with vincristine-treated BLQ1-VX-Tx.

Data published in Mol Cancer Thel;9(5) 1318-1327 using our producht.

S1134 AT9283 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 11

S1171 CYC116 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 7

S1249 JNJ-7706621Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 21

S2158 KW 2449 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 15

S1107 PHA-739358Synonyms:Synonyms: ZM Danusertib 252868, AG 1517, Tyrphostin AG 1517 Page 11 Ksp (Kinesin spindle protein)

S1452 Ispinesib Synonyms: SB-715992, CK0238273 Size Price

NH2 Ispinesib mesilate is an agent which inhibits the mitotic kinesin KSP with a Ki of 0.6 nM and has cytotoxic 10mg activity at less than 10 nM in a spectrum of tumor cell lines. Ispinesib mesilate is a potent inhibitor of kinesin O N H N Cl spindle protein. In vivo, Ispinesib mesilate enhanced the antitumor activity of trastuzumab, lapatinib, 50mg

N doxorubicin, and capecitabine and exhibited activity comparable with paclitaxel and ixabepilone. O 200mg

S2182 SB 743921 Size Price

SB743921 is a second generation, highly potent and active KSP inhibitor with a Ki of 0.1 nM for KSP (Eg5). It O 10mg is 5-fold more potent against the ATPase activity of KSP than ispinesib. It has cytotoxic activity at less than 2 Cl O nM is a spectrum of tumor cell lines. It is negative in a mouse model of peripheral neuropathy in which 50mg O N NH2 HCl paclitaxel is positive. 200mg

 Solutions to Signal Transduction Research MAPK

Multicellular organisms have three well-characterized subfamilies of mitoge- nactivated protein kinases (MAPKs) that control a vast array of physiological processes. These enzymes are regulated by a characteristic phosphorelay system in which a series of three protein kinases phosphorylate and activate one another. The extracellular signal-regulated kinases (ERKs) function in the control of cell division, and inhibitors of these enzymes are being explored as anticancer agents. The c-Jun amino-terminal kinases (JNKs) are critical regulators of transcription, and JNK inhibitors may be effective in control of rheumatoid arthritis. The p38 MAPKs are activated by inflamma- tory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity.

Several structural studies focused on p38 bound to the pyridinyl imidazoles VK19911, SB203580, SB216995, SB218655 and SB220025, compounds that bind in the ATP binding pocket of p38. The amino acid residue in the position equivalent to 106 of human p38 is crucial for determining the sensi- tivity of protein kinases to these inhibitors.

The development of MEK1 and MEK2 inhibitors has also progressed. Struc- tural information is particularly important for this class of kinase inhibitors because two of these inhibitors, PD98059 and U0126, do not appear to com- pete with ATP and thus are likely to have a distinct binding site on MEK. Enhanced MEK1 and MEK2 activity was detected in a significant number of primary human tumor cells. Thus, MEK1 and MEK2 inhibitors are being developed as therapeutic agents for the treatment of cancer.

Pharmacological inhibitors of MAPK pathways. Jessie M. English, Melanie H. Cobb. Trends Pharmacol Sci, 2002(23):40-45.

Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK and p38 Protein Kinases. Gary L. Johnson, et al. Science. 2002(298):1911-1912

 Papers Using Selleck Products

S1008 AZD6244(Selumetinib) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Ramin Nazarian et al. Nature, 2010(468): 973–977

Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma. Saadia A. Aziz et al. Clin Cancer Res, 2010(16):6029-6039.

Activation of FOXO3a Is Sufficient to Reverse Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor Chemoresistance in Human Cancer. Jer-Yen Yang et al. Cancer Res, 2010(70):4709

MEK1 mutations confer resistance to MEK and B-RAF inhibition. Caroline M. Emery et al. PNAS, 2009;106(48):20411-20416

S1020 CI-1040 (PD184352) BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Corcoran RB et al. Sci Signal, 2010; 3(149):ra84.

S1036 PD0325901 RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Iverson C et al. Cancer Res, 2009;69(17):6839-6847.

BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Corcoran RB et al. Sci Signal, 2010;3(149):ra84.

S1177 PD98059 Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells. Arana-Argáez VE et al. J Biol Chem, 2010;285(43):32824-32833

S1102 U0126-EtOH Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor. Molly M. McFarland-Mancini et al. J Immunol, 2010;184(12): 7219-7228.

 3+1 MAPK

MEK (MAPK/Erk kinase)

S1475 AS703026 Synonyms: MSC1936369B Size Price

OH H AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma. AS703026 10mg O N OH F H inhibited growth and survival of MM cells (cell IC50 ranging from 0.005 to 2 μM) and cytokine-induced N osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by 25mg AS703026 was mediated by G0-G1 cell cycle arrest and was accompanied by reduction of MAF oncogene I N expression. 50mg S2134 AZD8330 Synonyms: ARRY-424704, ARRY-704 Size Price H O N OH F O AZD8330 is an orally active, selective MEK inhibitor with potential antineoplastic activity. It specifically inhibits 10mg H N MEK, resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key 50mg N component of the MAPK signaling pathway that regulates cell growth. Constitutive activation of this pathway I has been implicated in many cancers. 200mg O S1008 AZD6244 Synonyms: ARRY-142886, Selumetinib, ARRY142886 Size Price

H 5mg HO N O MAPK kinase , immediately downstream of BRAF, is a promising target for ras-raf-MEK-ERK pathway O Cl H inhibition. Four lines bearing V600E BRAF mutations were all sensitive to AZD6244, with GI50 values ranging 10mg N from 14 to 50 nM. A positive control BRAF mutant melanoma line, SKMel28, exhibited a similar GI50 of 23 nM. 50mg Feed S1008 AZD6244 N F Br N lysatesfromvariouscancer celllines: breastcancer(MDA-MB-435),coloncancer(HCT116,SW620,andHT29), |!'_?ƒ 'š;› #<<|")Œƒ for4hweresubjectedtoimmunoblottingwiththeindicatedantibodies.

Data from Cancer Research.June 15 using our product. S1530 BIX 02188 Size Price

^}°"‘‘']}~]"*"$‘/$")'$}** 10mg

N N of flow. The physiological roles of Erk5 in neuronal cells have not been clarified. One reason was the lack of a H selective Erk5 pharmacological inhibitor until the novel selective MEK5/Erk5 inhibitors BIX02188 and 50mg H O N N BIX02189. H O 200mg

S1020 CI-1040 Synonyms: PD184352 Size Price O 5mg O CI-1040 is a non-competitive inhibitor of MEK1/2 with a Ki of 300nM in vitro CI-1040 inhibited MEK (as N measured by phosphorylated ERK (p-ERK) levels) with a half-maximal inhibitory concentration of 100–500nM H in all cell lines tested. 25mg F NH F Cl 200mg 600 Feed S1020 CI-1040 500 The bar chart represents the relative numbers of third-round colonies 400 of primary hematopoietic cells transduced with MLL-AF9 with treatment I 300 of compound PD184352 (CI-1040, 10uM, a MEK inhibitor) and SB216763 200 (10uM, GSK-3 inhibitor). The synergiceffect between compounds CI-1040

100 and SB-216763 has been observed.

Numbers of colonies of Numbers 0 Data from our customer Dr Dong Shou, Baylor College of Medicine. Control SB216763(10uM) PD184352(10uM) PD184352 + SB216763

S1531 BIX 02189 Size Price

BIX 02189 is a selective MEK5/ERK5 inhibitor with an IC50 of 59 nM. It inhibited catalytic function of purified, 10mg N N MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of H ERK1/2 in sorbitol-stimulated HeLa cells. The compounds also inhibited transcriptional activation of MEF2C, 25mg O N N a downstream substrate of the MEK5/Erk5 signaling cascade, in a cellular trans-reporter assay system. 200mg H O S1561 BMS 777607 Size Price

O ^'#"'€'}}~]"*®"$)'$}** 10mg H F N N on tumor cell growth but inhibited cell scattering activated by exogenous HGF, with almost complete inhibition "$])Œ„~? Ÿ<]$'Z*^'#" O O 50mg O F HGF-stimulated c-Met autophosphorylation and downstream activation of Akt and extracellular Cl signal-regulated kinase. 200mg

H2N N

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 MAPK 3+1V3'61

S1036 PD0325901 Size Price

H PD0325901 is non-competitive with ATP and is exquisitely specific and highly potent against purified MEK, N O 5mg HO O F exhibiting a Kiapp of 1 nM against activated MEK1 and MEK2. PD0325901 is roughly 500-fold more potent H than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, exhibiting OH N 25mg subnanomolar activity.

F I Feed S1036 PD0325901 50mg F Western blot analysis of p-Erk1/2, total Erk1/2, PD0325901 treated HT29 xenograft tumours.

Data provided by our customer Dr.Deborah Citrin,NIH.

S1568 PD318088 Size Price OH H N O PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor. It is a small-molecule inhibitor bound within 10mg O F H the allosteric site. The binding modes of two kinase inhibitors are shown in relation to the binding site of ATP OH N in the kinase active site. The MEK1 inhibitor PD318088 binds with ATP in a region of the kinase active site that 50mg is adjacent to the ATP-binding site. Br F I 200mg F S1102 U0126-EtOH Size Price

U0126 is an inhibitor of both MEK1(IC50 of 72 nM) and MEK2(IC50 of 58 nM). U0126 is a highly selective 25mg CN NH2 inhibitor of both MEK1 and MEK2. U0126 was found to functionally antagonize AP-1 transcriptional activity via S noncompetitive inhibition of the dual specificity kinase MEK with IC50 of 72 nM for MEK1 and 58 nM for MEK2. 100mg S U0126 sensitized MDA-MB231 and HBC4 to anoikis, i.e., upon treatment with U0126, cells deprived of NH2 CN NH2 anchorage entered apoptosis. 200mg NH2 Feed S1102 U0126-EtOH

OH Total and p-ERKs were assessed in small wounds generated in WTand Il6ra2/2 mice treated topically with vehicle(DMSO) or with the MEK inhibitor U0126. Wounds were harvested after 1 d, and western blotting was performed on lysates. Data from The Joumal of Immunology.May 10 2010 using our product. S1177 PD98059 Size Price O PD 98059 is a highly selective inhibitor of MEK1 and MEK2 with IC50 values of 4 μM and 50 μM respectively. 10mg PD98059 does not inhibit activation of other highly related dual-specificity protein kinases or the activity of over NH 2 18 other Ser/Thr protein kinases. At concentrations up to 100 μM, PD98059 does not inhibit activation of MKK3 50mg O or SEK (MKK4) as determined by measuring phosphorylation at its activation site. O 200mg Feed S1177 PD98059 ?~ƒ***‚„ _‘"]_|Z]Z")'ƒ was evaluated in SRP72 immunoprecipitated cell lysates. WB using anti-phosphoserine antibody showed a decreased ‚„€*)' <"Z])'"")'"<" (lanes 3,5,8 and 9). 3 D) Results were analyzed and RUA graphicated, **€)'<""Z])'"" ")'""$ Data from JBC.August 19, 2010 using our product. p38 MAPK (P38 mitogen-activated protein kinases)

S1574 BIRB 796 Synonyms: BIX02188 Size Price

BIRB 796 is a small molecule p38 MAPK inhibitor with an Kd of 0.1 nM. It is more potent than SB 203580 on O 5mg O N ?‘?‘';„“}***$^}‚^_# N O N N N baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing 10mg H H cytotoxicity and caspase activation. 50mg

 Solutions to Signal Transduction Research V3'61 MAPK

S1077 SB 202190 Size Price

N In the presence of SB202190, the ED50 values for the farnesyltransferase inhibitor FPT inhibitor II and MEK 25mg inhibitor U0126 were significantly decreased. SB202190 increased the phosphorylation of C-Raf and extracellular regulated kinase. SB202190 suppressed the kinase activity of p38, leading to inhibition of 50mg NH activation of MAPKAPK2. SB202190 blocked p38 half maximally at 30 nM, concentrations as high as 30,000 nM did not inhibit ERK and JNK activity. 100mg N OH Feed S1077 SB 202190 F ¦€^"_"Z]Z") and a decreased SRP72 expression was found when using ")'|‘_ƒ$ Data from JBC.August 19, 2010 using our product.

S1494 LY2228820 Size Price

N NH2 H N LY2228820 is a novel and potent p38MAPK inhibitor: in vitro kinase enzyme activity showed that the IC50 for N N 10mg

N ?‘';„?‘';„'?'ZZ*?‘';„Z?‘';„ panel of 172 additional kinases was more than 20 μM. Phosphorylation of MAPKAPK2 and/or HSP27, F 50mg downstream targets of p38 MAPK, was significantly inhibited by LY in both MM cell lines and LT-BMSCs. O O S OH S OH 200mg O O S1076 SB 203580 Synonyms: RWJ 64809, PB 203580 Size Price

SB 203580 is a potent inhibitor of LPS-induced cytokine synthesis in the human monocyte cell line THP-1 25mg N H O (IC50 = 50-100 nM). SB 203580 inhibited the RK from heat-shocked HeLa cells and osmotically stressed N S „~–~^„}~]"*"$#)'$^"?]‘"€*‚* 50mg independent of stress-activated protein kinase 2a/p38 inhibition. N Feed S1076 SB 203580 100mg

***?‘^"?]‘"|Z]Z")'ƒ‚„ F expression was evaluated by WB using antibodies against human SRP72, SRP54 and GAPDH. A decreased intensity of SRP72 bands were noted €])'<"|#ƒ ")'"<"|‘_ƒ$ Data from JBC.August 19, 2010 using our product.

S1527 Vinorelbine Synonyms: Navelbine Size Price

Vinorelbine is the first 5´NOR semi-synthetic vinca alkaloid and an anti-mitotic chemotherapy drug. In the 10mg O N O N H breast cancer cell lines MCF-7 and MDA-MB-468, increased p38 activity was demonstrated following O H O vinorelbine but not doxorubicin treatment, whether vinorelbine was given prior to or simultaneously with 50mg NH O doxorubicin. MAPK activity and p53 expression remained unchanged following vinorelbine treatment. O N HO O 200mg

S6005 VX-702 Size Price O F †°"€*}Œ#Z}Œ\|}~]" ]_Z__Z 25mg NH2 respectively). Platelet function alone, or in conjunction activation was completely or partially inhibited by

N N €)'*†°"|}~]" <"'ƒ$†°"**€ 50mg F H N O F F by any of the p38 MAPK agonists. 2 100mg S1458 VX-745 Size Price

N O VX-745 is a lead anti-inflammatory candidate, p38 MAPK inhibitor (IC50=10 nM) for the treatment of 10mg Cl Rheumatoid arthritis (RA). In vitro, VX-745 was selective for p38 MAPK compared to a large panel of kinases F F N N |}~]"1"3'ƒ$†°<]?‘';„|}~]" "'ƒZ?‘';„|}~]" "'ƒZ€ 50mg ?‘';„|}~]"1"3'ƒ$}Z*†°<]}~]"€*]#]'*}Œ S Cl \Z$ 200mg

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 MAPK (8GL041

S1104 GDC-0879 Size Price

GDC-0879 is a highly selective, novel potent, orally bioavailable B-Raf inhibitor in various in vitro and N 1mg HO cell-based assays with an IC50 estimate of 0.13 nM against purified B-Raf V600E enzyme and a cellular pErk OH N IC50 of 63 nM in the MALME-3M cell line. For this compound, subnanomolar enzyme potency translated into 5mg N very effective reduction of cellular viability of BRAF-mutant Malme3M cells (EC50 values were 0.75 μmol/L for GDC-0879). 10mg Feed S1104 GDC-0879

N B-RafV600E mutated melanoma line,A375,was treated with different doses of GDC0879 for 1h or 24 h. Cell lystates were analyzed by Western blotting to determine the leves of phosphorylated MEK1/2 (pMEK1/2) and phosphorylated ERK1/2 (pERK1/2)

Data provided by our customer Jong-in Park,Ph.D.,Medical College of Wisconsin

S1267 PLX-4032 Synonyms: RG7204, R7204, RO5185426 Size Price

F 10mg Cl O PLX4032 is a highly selective inhibitor of b-Raf kinase activity, with an IC50 of 44 nmol/L against O V600E-mutant b-Raf. b-Raf mutant melanoma cell strains were highly sensitive to PLX4032 with IC50 in the HN S 50mg F '|#"M<]"'ƒZ^‚;Z}~]"$<)'$ O N N H 200mg S1152 PLX-4720 Size Price F PLX4720 inhibits B-Raf V600E with an IC50 of 13 nM. PLX4720 preferentially inhibits the active B-Raf V600E O 5mg O kinase compared with a broad spectrum of other kinases (IC50:B-Raf=160 nM, BRK=130 nM, other kinases Cl N S ”"""'ƒZ–**–€†#""|}]"®$)'Z F 10mg H O }]"”")'ƒ$ N N 25mg H Feed S1152 PLX-4720

a dose titration of PLX-4720 in A375 melanoma cells which possess a V600E B-Raf mutation. Effects of increasing PLX-4720 dose on Erk phosphorylation and on tumor cell proliferation as determined by MTS assay are shown.

Data provided by Daniel C. Cho, MD Instructor, Harvard Medical School Director, Experimental Therapeutics Program Division of Hematology and Oncology Beth Israel Deaconess Medical Center

S2161 RAF265 Synonyms:Synonyms: ZMCHIR-265 252868, AG 1517, Tyrphostin AG 1517 Page 8

S1040 Sorafenib TosylatSynonyms:Synonyms: ZMNexavar, 252868, Bay 43-9006 AG 1517, Tyrphostin AG 1517 Page 9

S1178 BAY 73-4506Synonyms:Synonyms: ZMRegorafenib 252868, AG 1517, Tyrphostin AG 1517 Page 8

JNK(Jun N-terminal kinase)

S1460 SP600125 Size Price O SP600125 is a JNK inhibitor (IC50=40 nM for JNK-1 and JNK-2 and 90 nM for JNK-3). This agent exhibits 25mg greater than 300-fold selectivity for JNK against related MAP kinases Erk1 and p38–2, and the serine threonine kinase PKA. SP600125 is a reversible ATP-competitive inhibitor. In cells, SP600125 dose 50mg *¦€Z–*\~š°Z}ŒZ}\Z \$ 500mg N NH

 Solutions to Signal Transduction Research PI3K/Akt

Phosphoinositide 3-kinases (PI3Ks) catalyze the synthesis of the phosphati- dylinositol (PI) second messengers PI(3)P, PI(3,4)P2, and PI(3,4,5)P3. In the appropriate cellular context, these three lipids control diverse physiological processes including cell growth, survival, differentiation, and chemotaxis. The PI3-K family comprises 15 kinases with distinct substrate specificities, expression patterns, and modes of regulation.

The class I PI3Ks (p110a, p110b, p110d, and p110g) are activated by tyrosine kinases or G protein-coupled receptors to generate PIP3, which engages downstream effectors such as the Akt/PDK1 pathway, the Tec family kinases, and the Rho family GTPases. The class II and III PI3-Ks play a key role in intracellular trafficking through the synthesis of PI(3)P and PI(3,4)P2. The PIKKs are protein kinases that control cell growth (mTORC1) or monitor genomic integrity (ATM, ATR, DNA-PK, and hSmg-1).

A Pharmacological Map of the PI3-K Family Defines a Role for p110a in Insulin Signaling. Zachary A. Knight et al. Cell, 2006(125):733–747.

 Papers Using Selleck Products

S1009 BEZ235(NVP-BEZ235) Activation of FOXO3a Is Sufficient to Reverse Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor Chemoresistance in Human Cancer. Jer-Yen Yang et al. Cancer Res, 2010(70):4709

Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39. Kong D et al. Eur J Cancer. 2010;46(6):1111-1121.

Correlating Phosphatidylinositol 3-Kinase Inhibitor Efficacy with Signaling Pathway Status: In silico and Biological Evaluations. Shingo Dan et al. Cancer Res, 2010(70):4982

S1065 GDC-0941 Vertical inhibition of the mTORC1/mTORC2/PI3K pathway shows synergistic effects against melanoma in vitro and in vivo. Werzowa J et al. J Invest Dermatol, 2011;131(2):495-503.

S1022 Deforolimus(MK-8669) Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease. Ashe KM et al. Mol Genet Metab, 2010;100(4):309-315

S1120 Everolimus(RAD001) Pharmacodynamic Characterizationof the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma. Tap WD et al. Neoplasia, 2010;12(8):637-649.

S1226 KU-0063794 The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts. Jizhong Cheng et al. Circulation Res, 2010(107):1265-1274.

S1044 Temsirolimus Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease. Ashe KM et al. Mol Genet Metab, 2010;100(4):309-15.

 6/1 PI3K/Akt

PI3K

S1360 GSK1059615 Size Price

N "]_#]„}?€}~]"*„}?|"$<'ƒ„}?|"$# 10mg 'ƒ|]'ƒZ|'ƒš‚|'ƒ$"]_#] O PI3K pathway in cells inducing G1 arrest, although apopto-sis was observed in a subset of cell lines. Breast 50mg HN tumor cells seem to be more sensitive to this compound. S N 200mg O We treated all of drugs in T47D which has a PIK3CA H1047R Feed S1360 GSK 1059615 mutation with the concentration shown below for 1 hour and P-AKT DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 performed western blot analysis using antibodies to phospho-AKT P-AKTP (S473) Western blot analysis of Akt and p-Akt, (serine 473), and total AKT. 5uM AS-605240, 3uM GDC-0941, AKT AKT "")'"]_#]$ 4uM GSK1059615, 10uM LY294002, 8uM PI-103, 3uM PIK-90, DMSO PIK-90 TG100-115 TGX-221 ZSTK474

"3' "$3' 3' "3' "3' "3' 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. P-AKTP (S473) GSK1059615 Produced Independently by our customer Dr.Zhang, Data from our customer Dr.Saraswati Sukumar, AKT +++++-EGF(100ng/ml) Tianjin Medical University Johns Hopkins University School of Medicine. S1268 IC-87114 Size Price

O }~‘<**„}?$¶€•€"|}~]" "$?3'ƒ 1mg N """""*}„}?|"Z" N N "ƒ$*}~‘<€;„ 10mg N N of the class I PI3Ks are highly conserved. N 50mg H2N S1105 LY294002 Size Price

LY 294002 has been shown to be a potent inhibitor of PI3K activity, acting as a competitive inhibitor for ATP 10mg O binding site of the enzyme. LY 294002 inhibits cell proliferation of choroidal melanoma OCM-1 cells, the IC50 €")'$Œ_<""*}}$;*Œ_<""€ 25mg €*'„„*¶€|]")'ƒ*€€€¬€$ 50mg O N Feed DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1105 LY294002 O P-AKTP (S473) AKT We treated all of drugs in T47D which has a PIK3CA H1047R mutation with the concentration shown below for 1 hour and performed western blot analysis using antibodies to phospho-AKT (serine 473), and total AKT. DMSO PIK-90 TG100-115 TGX-221 ZSTK474 P-AKTP (S473) 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. AKT Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine. S1038 PI-103 Size Price

O PI-103 is a potent, cell-permeable, ATP-competitive PI3K family members inhibitor with IC50 of 2, 8, 20, 26, 10mg <‘Z ‘?Z ‘‘Z ]" ' * \;„Z "Z š‚~Z „}?~Z "Z š‚~Z "Z "Z respectively. PI-103 was essentially cytostatic for cell lines and induced cell cycle arrest in the G1 phase. 50mg N PI-103 had additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells. O N 200mg N Feed OH DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1038 PI-103 N P-AKTP (S473) AKT We treated all of drugs in T47D which has a PIK3CA H1047R mutation with the concentration shown below for 1 hour and performed western blot analysis DMSO PIK-90 TG100-115 TGX-221 ZSTK474 using antibodies to phospho-AKT (serine 473), and total AKT. P-AKTP (S473) 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, AKT 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine. S1410 AS-605240 Size Price O HN ;#"]<"„}?|}~]"‘'ƒZ?"*„}?„}? 10mg O S $]*„}?$*–*„}?Z€ block neutrophil chemotaxis in vitro and in vivo. In passive mouse models for rheumatoid arthritis these 50mg N compounds minimized progression of joint destruction. 100mg N We treated all of drugs in T47D which has a PIK3CA H1047R P-AKT Feed S1410 AS-605240 mutation with the concentration shown below for 1 hour and DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 performed western blot analysis using antibodies to phospho-AKT P-AKTP (S473) Western blot analysis of Akt and p-Akt, (serine 473), and total AKT. 5uM AS-605240, 3uM GDC-0941, AKT AKT "")';#"]<"$ 4uM GSK1059615, 10uM LY294002, 8uM PI-103, 3uM PIK-90, DMSO PIK-90 TG100-115 TGX-221 ZSTK474 "3' "$3' 3' "3' "3' "3' 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. AS-605240 P-AKTP (S473) Produced Independently by our customer Dr.Zhang, Data from our customer Dr.Saraswati Sukumar, +++++-EGF(100ng/ml) AKT Tianjin Medical University Johns Hopkins University School of Medicine.

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 PI3K/Akt 6/1

S1462 AZD6482 Size Price

O ;› #<‘„}?|}~]" "$")'ƒ€$ N 10mg that is critical to pathological thrombus formation without interfering with normal haemostasis, which avoids the N N O *–$„}?}~]"*"$"Z$

S1009 BEZ235 Synonyms: NVP-BEZ235 Size Price

NVP-BEZ235 inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. 25mg N The PI3K/Akt/ mTOR pathway is often constitutively activated in human tumor cells. For Class I PI3K family, O N \†„^›?]}~]"<'"Z]'"Z'"Z]' 100mg N N "$œ€**<?;?"‘„;]"’€€€ concentration of 8.0 and 30 nmol/L. 200mg N

Feed S1009 BEZ235

„}?}~]"€$ Relative kinase activities of '"")'›<

O ° Z Z * „}? "$ – € 5mg ° Œ_<"" €Z  „}? * $ ° O N Z€"""*„}?Z$ 25mg N N ° * € „}|?Z<ƒ„ € }}? adhesion in platelets. 100mg H N Feed DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1169 TGX-221 P-AKTP (S473) AKT We treated all of drugs in T47D which has a PIK3CA H1047R mutation with the concentration shown below for 1 hour and performed western blot analysis DMSO PIK-90 TG100-115 TGX-221 ZSTK474 using antibodies to phospho-AKT (serine 473), and total AKT. P-AKTP (S473) 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, AKT 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine.

S1118 XL147 Synonyms: SAR245408 Size Price

N S N XL147 is a selective inhibitor of Class I PI3K isoforms. XL147 reversibly binds to class 1 PI3Ks in an 5mg

ATP-competitive manner, inhibiting the production of PIP3 and activation of the PI3K signaling pathway. XL147 exhibits dose-dependent and sustained inhibition of PI3K signaling in multiple human tumor xenograft 10mg N NH models when administered as a single agent. 50mg N NH Feed S1118 XL147 O S O

Western blot analysis of Akt and p-Akt, "])'°Œ<$

Produced Independently by our customer Dr.Zhang, Tianjin Medical University

 Solutions to Signal Transduction Research 6/1 PI3K/Akt

S1523 XL765 Synonyms: SAR245409 Size Price

O °Œ#]–š‚„}?}~]"*]Z?_Z?Z_

S1072 ZSTK474 Size Price

O ›<<*„}?|}~]"#'ƒ$„}?„}?}~]"* 50mg 53 nM, respectively. ZSTK474 was identified from a chemical library of about 1500 triazine derivatives, and N selected for their ability to block tumor cell growth. Toxicity was reported to be moderate. 200mg F N N F Feed DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1118 XL147 1g N N N N P-AKTP (S473) We treated all of drugs in T47D which has a PIK3CA H1047R mutation with O AKT the concentration shown below for 1 hour and performed western blot analysis using antibodies to phospho-AKT (serine 473), and total AKT. DMSO PIK-90 TG100-115 TGX-221 ZSTK474 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, P-AKT (S473) 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. AKT Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine.

S2207 PIK-293 Synonyms: AS605240 Size Price

NH2 1(: N „}_? „}? $„}_? "Z"Z"， " }~]" * 10mg 100uM,25uM,0.24uM,and 10uM.PIK-293 is the parent compand of PIK-294. N N N N 50mg

N 200mg O

S1187 PIK-90 Size Price

N „}_"„}?Z}~]"€|'ƒ*Z?]"Z‘Z]‘*"Z 5mg N Z*Zš‚$^†‘‘[Z„}_"€ hydrophobic affinity pocket of the ATP binding site, where it also interacts with Lys833. 10mg O N NH O O N 50mg Feed DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1187 PIK-90 P-AKTP (S473) AKT We treated all of drugs in T47D which has a PIK3CA H1047R mutation with the concentration shown below for 1 hour and performed western blot analysis using antibodies to phospho-AKT (serine 473), and total AKT. DMSO PIK-90 TG100-115 TGX-221 ZSTK474 PP-AKT (S473) 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. AKT Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine. S1489 PIK-93 Size Price

HO Cl 1mg NH „}_?„}<}}}|}~]"_'ƒ$„}_?*„}<Z S O N „}<}}}$}Z€„}?|}~]" O S #'ƒ$€"Z"Z"}~]"*"$"?_Z"$]_Z"$3'$ 5mg NH O 25mg

S1352 TG100-115 Size Price

OH ""]Z„}?M|}~]"€*‘??]'ZƒZ„}? 10mg  €** |}~]" €” )'ƒ$ ; € * *Z ""] NH2 ??Z*}~]"€®)'$ 50mg N N Feed 200mg DMSO AS-605240 GDC-0941 GSK1059615 LY294002 PI-103 S1352 TG100-115 N N NH2 P-AKTP (S473) AKT We treated all of drugs in T47D which has a PIK3CA H1047R mutation with the concentration shown below for 1 hour and performed western blot analysis OH using antibodies to phospho-AKT (serine 473), and total AKT. DMSO PIK-90 TG100-115 TGX-221 ZSTK474 5uM AS-605240, 3uM GDC-0941, 4uM GSK1059615, 10uM LY294002, P-AKTP (S473) 8uM PI-103, 3uM PIK-90, 4uM TG100-115, 5uM TGX-221, 3uM ZSTK474. AKT Data from our customer Dr.Saraswati Sukumar,Johns Hopkins University School of Medicine.

?_œ€ Synonyms: Z'Zœ€ Page 12

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 PI3K/Akt S:58

mTOR (Mammalian target of rapamycin)

S1039 Rapamycin Synonyms: Sirolimus, Rapamune Size Price

HO RAPA administration prevented the rejection of the donor graft, accelerated post-BMT hematopoietic 50mg O recovery, and did not compromise recipient survival. In vitro, rapamycin inhibited the proliferation of primary bone marrow cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in cell-conditioned 200mg media. O O OH N 500mg Feed O O O S1039 Rapamycin O O HO O O Western blot analysis of mTOR and p-mTOR, ")'‚€$ Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1044 Temsirolimus Synonyms: Torisel, CCI-779 Size Price

HO OH O O Temsirolimus is a recently developed mTOR inhibitor, with improved aqueous solubility and more favorable 25mg O pharmaceutical properties compared with the parent compound rapamycin. Temsirolimus has shown

O O OH H O promising preclinical and early clinical antitumor activity and is currently in phase III clinical development for 50mg O N O O the treatment of different solid tumors. OH H O O 200mg O S1266 WYE-354 Size Price O 10mg N WYE-354,a cell-permeable pyrazolopyrimidine compound,is a potent and ATP competitive inhibitor of mTOR

N |}~]" ]'ƒZ*„}?*|”""*ƒ$!¬€ N O N N nude mice, WYE-354 inhibited mTORC1 and mTORC2 and displayed robust antitumor activity in PTEN-null 50mg O N H tumors. N 200mg O O

S1226 KU-0063794 Size Price

O Ku-0063794 is a specific inhibitor of mTOR, which inhibits both mTORC1 and mTORC2 with an IC50 of 5mg N approximately 10 nM, but does not suppress the activity of 76 other protein kinases or seven lipid kinases, 10mg N including Class 1 PI3Ks at 1000-fold higher concentrations. Ku-0063794 also suppressed cell growth and induced a G1-cell-cycle arrest. N N N 50mg O Feed O S1226 KU-0063794

OH Mechanical stretch–induced SGK-1 activation is dependent on IGF-1R and mTORC2 signaling pathway.mTORC2-mediated stretch-induced SGK-1 phosphorylation. SMCs infected with Ad-SGK-1 were pretreated with PPP (10 umol/L), rapamycin (100 nmol/L),or Ku-0063794 (10 umol/L) for 30 minutes and then were subjected to stretch or IGF-1 (10 ng/mL) for 30 minutes.

Data from Circulation Research using our product. S1555 AZD8055 Size Price O AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mTOR kinase inhibitor with an IC50 5mg N of 0.8 nM. It inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as N phosphorylation of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 10mg HO N N N phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in significant inhibition of O O cap-dependent translation. 25mg

S1022 Deforolimus Synonyms: AP23573, MK-8669, Ridaforolimus Size Price

P O O O Deforolimus is a small-molecule inhibitor of mTOR. It is an immunosuppressant for the treatment of certain 10mg cancers. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, O O OH H O O metabolism, and angiogenesis. 50mg N O O OH H O O O 200mg Feed S1022 Deforolimus

Concentration-time profile in rat serum following Western blot analysis of mTOR and p-mTOR, administration of deforolimus formulations ")'‚€$ (10 mg/kg) intravenously to rats (mean ± SEM). Produced Independently by our customer Dr.Zhang, Data from our customer Neal M. Davies,Department of Tianjin Medical University Pharmaceutical Sciences, Washington State University, Pullman, Washington

 Solutions to Signal Transduction Research S:58*4'61-916*1 PI3K/Akt

S1120 Everolimus Synonyms: RAD001, SDZ-RAD, Certican, Zortress, Afinitor Size Price

OH In cells, Everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an 5mg

O immunosuppressive complex that binds to and inhibits the activation of mTOR. Inhibition of mTOR activation

O results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, 25mg IL-4, and IL-15) stimulation and the inhibition of antibody production. 100mg O O OH N Feed S1120 Everolimus O O O O O HO O O Western blot analysis of mTOR and p-mTOR, ")'‚€$ Produced Independently by our customer Dr.Zhang, Tianjin Medical University

S1009 BEZ235 Synonyms:Synonyms: ZM NVP-BEZ235 252868, AG 1517, Tyrphostin AG 1517 Page 54

S1360 GSK1059615 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 53

S1038 PI-103 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 53

S1523 XL765 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 55

S2406 Chrysophanic acid Synonyms:Synonyms: ZM C hrysophanol,252868, AG NSC 1517, 37132, NSCTyrphostin 646567 AG 1517 Page 5 1(:

DNA-PK (DNA-activated protein kinase)

S1205 PIK-75 HCl Size Price

N „}][*"**„}?}~]"*#Z?""Z#Z]"'* 5mg N Br "Z"Z"Z"Z$^*„}?Z„}] \;„ N 10mg O NO2 IC50 of 2 nM, but not mTORC1 and mTORC2. PIK-75-mediated anti-inflammatory effects are associated with N S *;Z}\'^$ HCl O 25mg

S1523 XL765 Synonyms:Synonyms: ZM SAR245409 252868, AG 1517, Tyrphostin AG 1517 Page 55

GSK-3 (Glycogen synthase kinase)

S1263 CHIR-99021 Synonyms: CT-99021 Size Price

N N 5mg ~[}‚__"?*$~[}‚__" HN H Cl GSK-3 with IC50 at 7 nM. In a series of carcinoma cell lines, the IC50 of CHIR99021 for proliferation is about N N Cl 25mg ")'$~[}‚__"–~ ?]"*? N compared to CDKs . N 100mg HN S1075 SB 216763 Size Price O N ^##?€?}~]"*?<'Z*"$"';„$ 5mg NH ^##??;„$^##??*_'$ O }*"$';„Z")'^##??_#’$}Z 10mg Cl compounds exhibited little or no inhibition of the other 24 members of the kinase selectivity panel. 50mg Cl

PDK-1 (3-phosphoinositide-dependent protein kinase)

S1556 PHT-427 Size Price

PHT-427 inhibited Akt and PDPK1 signaling and their downstream targets in sensitive but not resistant cells 10mg

and tumor xenografts. When given orally, PHT-427 inhibited the growth of human tumor xenografts in €*Z€‘"’€Z 50mg analogues with C4, C6, or C8 alkyl chains. Inhibition of PDPK1 was more closely correlated to antitumor H 200mg N N activity than Akt inhibition. S N O S O

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 PI3K/Akt ':3'QZ

ATM (Ataxia telangiectasia-mutated protein kinase)

S1092 KU-55933 Size Price

O KU-55933 is an ATP-competitive inhibitor, inhibits ATM with an IC50 of 13 nmol/L and a Ki of 2.2 nmol/L. 5mg N O Exposure of cells to KU-55933 resulted in a significant sensitization to the cytotoxic effects of ionizing radiation and to the DNA double-strand break-inducing chemotherapeutic agents. Derivatives of this molecule may 10mg O serve as novel radio- and chemosensitizors in clinical settings. KU-55933 is capable of suppressing the replication of HIV-1. 50mg S

Feed S1092 KU-55933 S Effect of ATM inhibitor in etoposide-induced cell death. The cells were pretreated with KU55933 (2 nM) for 1 hr before etoposide treatment. Data from JBC. December 9, 2010 using our product.

S1570 KU-60019 Synonyms: Torisel, CCI-779 Size Price

O KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM 10mg O N targets in human glioma cells. A-T fibroblasts were not radiosensitized by KU-60019, strongly suggesting that S O O the ATM kinase is specifically targeted. Furthermore, KU-60019 reduced basal S473 AKT phosphorylation. 50mg N O N H 200mg

Akt

S1558 AT7867 Size Price

Cl NH AT7867 is a potent and oral AKT and p70 S6 kinase inhibitor with an IC50 of 17 nM. Administration of AT7867 10mg to athymic mice implanted with the PTEN-deficient U87MG human glioblastoma xenograft model caused inhibition of phosphorylation of downstream substrates of both AKT and p70S6K and induction of apoptosis. 50mg

200mg HN N

S1078 MK-2206 Size Price

H N 2HCl 2 MK-2206, a highly selective non-ATP competitive allosteric Akt inhibitor, has nM IC50. MK-2206 is a potent 5mg allosteric Akt inhibitor with IC50 at 8 nM, 2 mM, 65 mM for Akt1, Akt2 and Akt3 respectively. MK-2206 is N € #" œš  10mg N O preclinical models. HN N 25mg Feed S1078 MK-2206

Ÿ‘')''"#* ~|ƒ)''"#*Z 1 hr prior to IR, and then irradiated with 6 Gy. Total then irradiated with indicated dosage. 4 hr after IR, cells were fed cell lysate was harvested 1 hr after IR and subjected with drug-free medium, and incubated for another 20 hr at 37°C, to Western blot analysis with the indicated antibody. after which they were trypsinized and seeded for clonogenic Cells without IR treatment were used as a control. survival assay. Colony-forming efficiency was determined 14 d later.

Data from Radiation Oncology 2009, 4:43 using our product.

S1037 Perifosine Synonyms: KRX-0401, NSC 639966 Size Price

O- O P Perifosine inhibits Akt activation, targeting cellular membranes, modulates membrane permeability, 5mg O O membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic MAPK pathway and 10mg N+ modulates the balance between the MAPK and SAPK/JNK pathways, thereby inducing apoptosis. Feed 25mg 120 48 h treatment S1037 Perifosine HePC Edelfosine Inhibition curves in HepG2 cells exposed to Alkylphospholipid-induced morphological 100 ErPC Perifosine different concentrations of alkylphospholipids. changes in HepG2 cells. Cell morphology

80 Cells growing in log-phase were incubated with was examined with an inverted microscope ''"’^* (20¥ original magnification). The morphology 60 different concentrations of APLs for 48 h. Cell *[€''"’ (’ of control) (’ number was determined by the crystal violet FBS is shown in the absence of any addition. 40 staining assay and expressed as percentage Data from British Journal of Pharmacology of control (no addition) cells. 20 (2010), 160, 355–366 using our product. Cell growth Data from British Journal of Pharmacology (2010), 0 020406080160, 355–366 using our product. APL concentration (3'ƒ

S1556 PHT-427 Synonyms: ZM 252868, AG 1517, Tyrphostin AG 1517 Page 56

 Solutions to Signal Transduction Research Hormones

Steroid hormone receptors function classically as transcription factors. More recently, it has become apparent that steroid hormones also initiate nonge- nomic responses via activation of a subpopulation of these receptors that are non-nuclear. Estrogen activation of non-nuclear estrogen receptors, resulting in rapid signaling in cell types in culture as diverse as oocytes, osteoblasts, osteoclasts, breast cancer cells, adipocytes, and endothelial cells. However, because it is difficult to discriminate between extranuclear-initiated and nuclear-initiated ER actions, it remains unknown whether non-nuclear signal- ing by ER, or any other SHR, is operative and biologically relevant in vivo.

Androgens are important mediators of transcriptional pathways controlling the proliferation, differentiation, and apoptosis of normal and neoplastic pros- tate cells and play a critical role in the development and progression of pros- tate cancer. Androgen deprivation therapy (ADT) is considered standard systemic treatment for advanced prostate cancer, and is being increasingly used in neoadjuvant and adjuvant protocols for the treatment of high-risk, early-stage disease.

Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for astration-Resistant Prostate Cancer. Elahe A. Mostaghel et al. Cancer Res, 2007(67):5033 but not uterine or breast cancer growth in mice. Ken L. Chambliss et al. J Clin Invest, 2010;120(7):2319–2330

 Hormones 'TJXUMKT8KIKVZUX+YZXUMKT8KIKVZUX

Androgen Receptor

S1585 17 -propionate Size Price O HO 17 alpha-propionate is a new topical and peripherally selective androgen antagonist. Although it displayed a O 10mg strong local antiandrogenic activity in hamster’s flank organ test, it did not exhibit antiandrogenic activity in rats H O after subcutaneous injection, nor did it affect gonadotropins hypersecretion when injected to parabiotic rats. 50mg H H O 200mg S1140 Andarine Size Price

O Andarine (S-4) is an investigational selective androgen receptor modulator for treatment of conditions such as H 10mg N N+ O O- muscle wasting, osteoporosis and benign prostatic hypertrophy, using the non-steroidal androgen antagonist O F bicalutamide as a lead compound. Andarine is an orally active partial agonist for androgen receptors. It is less 50mg O N H F potent in both anabolic and androgenic effects than other SARMs. OH F 200mg S1190 Bicalutamide Synonyms: Casodex, Cosudex, Calutide, Kalumid Size Price

N F Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer and hirsutism. 50mg F F O Bicalutamide acts as a pure anti-androgen by binding to the androgen receptor (AR) and preventing the HN

OH activation of the AR and subsequent upregulation of androgen responsive genes by androgenic hormones. In 100mg O SO addition, bicalutamide accelerates the degradation of the androgen receptor. 200mg

F

S2460 Dehydroepiandrosterone Synonyms: DHEA Size Price O Dehydroepiandrosterone is a 19-carbon endogenous natural steroid hormone. It is the major secretory 100mg H steroidal product of the adrenal glands and is also produced by the gonads and the brain. It acts on the androgen receptor both directly and through its metabolites, which include androstenediol and 200mg H H androstenedione, which can undergo further conversion to produce the androgen testosterone and the HO estrogens estrone and estradiol. 250mg S1250 MDV3100 Size Price

F F O F MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor 10mg N and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces F N N H 50mg N S tumour cell apoptosis, and has no agonist activity.

O 200mg S1174 Ostarine Synonyms: GTx-024, MK-2866 Size Price

N N Ostarine, a non-steroidal agent, is selective androgen receptor modulator (SARM) with anabolic activity. This 10mg O F agent is designed to work like testosterone, thus promoting and/or maintaining libido, fertility, prostate growth, O N 50mg H F and muscle growth and strength. Mimicking testosterone’s action, this agent may increase lean body mass, OH F thereby ameliorating muscle wasting in the hypermetabolic state of cancer cachexia. 200mg

Estrogen Receptor

S1972 Tamoxifen Citrate Synonyms: Nolvadex, Istubal, Valodex Size Price

–*~|\–ƒ}~]"*?)'*'~$} 5mg

N some tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as O a mixed agonist/antagonist. It has been the standard endocrine (anti-estrogen) therapy for hormone-positive 10mg early breast cancer in pre-menopausal women, although aromatase inhibitors have been proposed. CO2H HO2C CO2H 25mg OH S1776 Toremifene Citrate Synonyms: Fareston, Acapodene Size Price

Cl Toremifene Citrate is an oral selective estrogen receptor modulator which helps oppose the actions of 25mg estrogen in the body. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator.

N O This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene 50mg also has intrinsic estrogenic properties, which are manifested according to tissue type or species. HO O O OH 100mg HO O OH

 Solutions to Signal Transduction Research +YZXUMKT8KIKVZUX'XUSGZGYK Hormones

S2466 Estriol Synonyms: Oestriol Size Price OH Estriol is a G-protein coupled estrogen receptor antagonist. It is one of the three main estrogens produced by 10mg H OH the human body. It may play a role in the development of breast cancer, but based on in vitro research does appear to act as an antagonist to the G-protein coupled estrogen receptor. 25mg H H HO 50mg

S1227 Evista Synonyms: Raloxifene Hydrochloride, keoxifene Size Price

OH 100mg S Raloxifene has estrogen and tamoxifen-like effects on bone and serum cholesterol levels in ovariectomized O $‚–**~]" "$?*–€ HO N skeleton. Raloxifene is demonstrated an extremely low IC50 value of 2.9 nM for phthalazine oxidase in human 200mg O .HCl liver cytosol. S1191 Fulvestrant Synonyms: Faslodex, ICI 182780 Size Price OH 25mg H Fulvestrant is a synthetic estrogen receptor antagonist or selective estrogen receptor down-regulator. H H HO Fulvestrant binds competitively to estrogen receptors in breast cancer cells, resulting in estrogen receptor 50mg deformation and decreased estrogen binding. Fulvestrant is used for the treatment of hormone receptor

S positive metastatic breast cancer in postmenopausal women with disease progression following O 100mg F anti-estrogen therapy. F F F F S2473 Hexestrol Synonyms: Bibenzyl, Cycloestrol, Dihydro-stilbestro, Dihydrostilbestrol, Estra-Plex Size Price OH [–*–Z;‚~;‚~ 100mg }~]"*"$‘Z_$]Z$‘3'Z–***$• potently inhibited by diethylstilbestrol, hexestrol and zearalenone. The inhibitory potencies of 200mg |}~]" $]3'ƒZ–|}~]" ?"3'ƒZ•|}~]" ?#3'ƒ*[ ] were lower than those for TBER1. 250mg

OH S1598 LY500307 Size Price

Œ]""?"Z~]"*"$##'$}|?*ƒ 10mg H H ‚*€*€‚‚|_"’**ƒ$Œ]""?" OH is a drug used to treat prostate diseases. 50mg HO O 200mg

Aromatase

S1188 Anastrozole Synonyms: Arimidex, AstraZeneca Size Price N N N Anastrozole inhibits the enzyme aromatase, which is responsible for converting androgens to estrogens. 50mg Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition. Elevated levels of estrogens may increase the severity of breast cancer, as sex hormones can cause hyperplasia and 100mg NC CN differentiation at estrogen receptor sites. 200mg

S1196 Exemestane Synonyms: Aromasin Size Price O Exemestane is an irreversible, oral steroidal aromatase inhibitor used in the adjuvant treatment of 25mg H hormonally-responsive breast cancer in postmenopausal women. Its structure was related to the natural substrate androstenedione and it acts as a false substrate for the aromatase enzyme. The estrogen 50mg H H €*–*‘]’*|ƒ_]’*|ƒ$– O found to inhibit human placental aromatase with IC50 of 42 nM. 100mg

S1235 Letrozole Synonyms: CGS 20267, Femara, Piroxicam Size Price CN N ~"#–€Œ[€€"$)' 10mg N N }~]" * "$" )' * ** € € ?]" )'$ } ;~[€ € Z € }~]" * " )' 50mg (10,000 times higher than the IC50 for estradiol production); no significant effect on corticosterone production

?]")'$ 100mg CN

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Hormones śXKJ[IZGYK-68

S1202 Dutasteride Synonyms: Avodart Size Price F F F F F Dutasteride is a 5-alpha-reductase inhibitor that inhibits the conversion of testosterone into dihydrotestosterone 10mg F HN O (DHT). Dutasteride inhibits both isoforms of 5-alpha reductase (5aR1 and 5aR2) to a similar extent (IC50

6nmol/l and 7 nmol/l, respectively), while finasteride only inhibits Type II. Dutasteride competed for binding the 25mg H Œ\~„;‚}~]"–$]3'$ H H O N 100mg H H S1197 Finasteride Synonyms: Proscar, Propecia Size Price

HN Finasteride, a synthetic 4-azasteroid antiandrogen compound, is a specific inhibitor of steroid Type II 5 200mg O €Z€• [$} H hyperplasia, finasteride inhibits 5-alpha-reductase activity in epithelium for Ki of 10nM, significantly lower than 1g

H H | ??'ƒ$ O N H H GPR (glycoprotein receptor)

S2149 GSK1292263 Synonyms: KRX-0401, NSC 639966 Size Price

O N O GSK1292263 is a novel GPR119 receptor agonist used for the treatment of type 2 diabetes. In the intravenous N 10mg N O S €Z*€€;Ÿ~|"]ƒ*?"#"’ N O were reported in the GSK1292263 treatment group, compared with values in the vehicle control cohort. 50mg

200mg

 Solutions to Signal Transduction Research Integrase/CCR5

Remarkable progress has been made since integrase was recognized as a rational therapeutic target for the treatment of HIV infection. The mechanism of inhibition by the specific strand-transfer inhibitors fits the model of interfa- cial inhibitors of protein–nucleic acid interactions, as these drugs block a tran- sition state of the integrase-DNA complex. Counterscreens with related enzymes, such as HIV RNase H, might be useful to assess the selectivity of integrase inhibitors, and could lead to the discovery of RNase H inhibitors that are therapeutically active against HIV and AIDS.

The chemokine receptor CCR5 serves as an essential cofactor for HIV entry and acquisition of infection. Thus, persons whose cells lack surface CCR5 expression because of mutation are almost completely protected from acquir- ing HIV infection. Furthermore, viruses that utilize CCR5 predominate in early stages of mucosal transmission, which suggests that mucosal transmission may selectively involve CCR5. Hence, inhibition of CCR5 has been proposed as a possible “microbicide” strategy for prevention of HIV infection.

- tion PIs, NNRTIs, integrase inhibitors and CCR5 antagonists. Amelia Hughes et al. J Infect, 2008(57):1e10 !"#$"""%- tion of CCR5. Michael M. Lederman et al. Science, 2004(306):485

 Papers Using Selleck Products

S2004 Vicriviroc Malate Potential of novel antiretrovirals to modulate expression and function of drug transporters in vitro. Nadine Cécile Luise Zembruski et al. J Antimicrob Chemother, 2011;66(4): 802-812.

S2001 Elvitegravir(GS-9137) Identification and Characterization of Persistent Intracellular Human Immunodeficiency Virus Type 1 Integrase Strand Transfer Inhibitor Activity. Yasuhiro Koh et al. Antimicrobial Agents and Chemotherapy, 2011; 55(1): 42-49

Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors. Robert A Smith et al. Retrovirology, 2010(7):70

Potential of novel antiretrovirals to modulate expression and function of drug transporters in vitro. Nadine Cécile Luise Zembruski et al. J Antimicrob Chemother, 2011;66(4): 802-812.

 ))8/TZKMXGYK Integrase/CCR5

CCR5 (C-C chemokine receptor type 5)

S2003 Maraviroc Synonyms: Selzentry, UK-427857, Celsentri Size Price

Maraviroc was active (IC90) at low nanomolar concentrations against HIV-1 Ba-L when measured in a 5-day F F 5mg €€|ƒ„^'~|}~_"Z?$'“_]’~}Z$"<$_ 'ƒZ„^'~|}~_"Z$‘'“_]’Z~}$$#'ƒ„'|}~_"Z$'“_]’~}Z"$< 25mg 1.7 nM). Maraviroc inhibited MIP-1 (IC50, 3.3 nM) and RANTES (IC50, 5.2nM) binding to cell membrane preparations of CCR5-expressing HEK-293. O NH 100mg Feed S2003 Maraviroc N N N N Maraviroc was added to the cells in the indicated concentrations 1 hour **]");„|Jƒ]"‚;\|[ƒ$;*< hours of cell stimulation, conditioned media were collected and analyzed for MMP-9 activity by the method of zymography

MMP Activity,percentage of control Data Provided by our customer Mikhail Menshikov, Cardiology Research Center Maraviroc concentration, 3' S2004 Vicriviroc Malate Size Price

Vicriviroc showed equally potent inhibition of the chemotactic response to MIP-1 with IC50 values below 1 nM. 5mg O Vicriviroc potently inhibited RANTES-induced signaling with mean IC50s of 4.2 nM. Vicriviroc is highly €*”‘_’$€ 10mg €€|C‘<’ƒ€–€$†\š; N p-glycoprotein Substrate in vitro. N N 50mg CF3 4 Feed N N * S2004 Vicriviroc Malate *

C4H6O5 3 * O * Effect of antiretrovirals and positive control rifampicin * (at 10 mmol/L) on ABCB1 function in LS180 cells after * 2 3 and 7 days (d) of treatment. ABCB1 function was normalized to the medium control . Data are to medium control 1 expressed as means+SEM for n¼4. **P,0.01. ABCB1 function normalized

0 Data from Journal of Antimicrobial Chemotherapy using our product.

mol/L) mol/L) mol/L) mol/L) mol/L) mol/L) mol/L) mol/L) μ μ μ μ μ μ μ μ

roc (10 oc (10 avir (10 vir (10 vi roc (10 r ra ra fampicin (10 d Rifampicin (10 d Ma d Maravirocd Vicrivir (10 3 d Vicrivi d Ri d Elvitegd Elviteg 7

Integrase

S1366 BMS-707035 Synonyms: BMS707035 Size Price O F HO 10mg N BMS-707035 is an HIV-1 integrase inhibitor. BMS-707035 was scheduled to be evaluated in a Phase II study H N to assess the antiretroviral activity, safety, pharmacodynamics, and pharmacokinetics in 50 HIV-infected N N 50mg subjects using a 10-day randomized, double-blind, placebo-controlled, ascending multiple-dose study design. O O S O 200mg S2005 Raltegravir Synonyms: MK-0518, Isentress, Raltegravir potassium Size Price O OH F N N N Raltegravir is a novel HIV-1 integrase strand transfer inhibitor with potent in vitro activity against wild-type and 5mg H H N N €[}†€|}~_]*[}†]"’€€ ??'ƒ$‚ O N 10mg O O not a potent inhibitor or inducer of cytochrome P450 3A4. 50mg S2001 Elvitegravir Synonyms: EVG, GS-9137, JTK-303 Size Price

EVG exerted potent anti-HIV activity against not only wild-type strains but also drug-resistant clinical isolates. 10mg Cl EVG also showed antiviral activity against murine leukemia virus and simian immunodeficiency virus. EC50 |'ƒ|[}†}}}^ "$Z[}†[š $‘Z[}†‚š $<ƒ†*[}† 50mg O O F used as a positive control for the luciferase assay (EC50 values of 0.8 nM), as observed in the MAGI assay HO with HIV-1IIIB. 200mg 4 Feed S2001 Elvitegravir N O * *

3 * * Effect of antiretrovirals and positive control rifampicin

* (at 10 mmol/L) on ABCB1 function in LS180 cells after OH * 2 3 and 7 days (d) of treatment. ABCB1 function was normalized to the medium control . Data are to medium control 1 expressed as means+SEM for n¼4. **P,0.01. ABCB1 function normalized

0 Data from Journal of Antimicrobial Chemotherapy using our product.

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Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  Phone:+1-832-582-8158 Proteases/HSP90/HSP70

The function of intracellular proteases in signalling cascades is generally associated with the removal of damaged or undesirable products. Lyso- somal cysteine and aspartyl cathepsins mediate the degradation of endocy- tosed proteins. The cysteine proteases of the caspase family function in a tightly regulated cascade of proteolytic activities those result in apoptosis.

Conversely, extracellular proteases are thought to be actively involved in facilitating tumorigenesis. These enzymes are frequently overexpressed in malignant tissues, often as a result of the activation of oncogenic transcrip- tional pathways. The prevailing view that proteases promote tumour progression and metastasis led to the development of small-molecule inhibi- tors for the treatment of cancer, in particular of molecules targeting matrix metalloproteinases (MMPs) and plasminogen activators. However, clinical trials

Small Heat Shock Proteins (sHSPs) are one of the least well understood classes of molecular chaperones, proteins which act to prevent or reverse improper protein associations. The importance of the sHSPs is evidenced by their almost ubiquitous expression, the presence of multiple sHSP genes in most organisms, and their dramatic up-regulation under stress conditions making them among the most abundant of cellular proteins. They are impli- cated in a range of disease states including cataract, cancer, myopathies, motor neuropathies, and neurodegeneration.

Emerging roles of proteases in tumour suppression. Carlos López-Otín et al. Nat Rev Canc, 2007(7):800-808 Quaternary dynamics and plasticity underlie small heat shock protein chaperone function. Florian Stengel et al. PNAS, 2010;107(5): 2007–2012

 Papers Using Selleck Products

S1013 Bortezomib The clinically approved proteasome inhibitor PS-341 efficiently blocks influenza A virus and vesicular stomatitis virus propagation by establishing an antiviral state. Dudek SE et al. J Virol, 2010; 84(18):9439-9451.

Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2. Schaedler S et al. J Biol Chem, 2010; 285(52):41074-41086

Secretory phospholipase A2-IIa is involved in prostate cancer progression and may potentially serve as a biomarker for prostate cancer. Zhongyun Dong et al. Carcinogenesis, 2010;31(11): 1948-1955.

Rotavirus Replication Requires a Functional Proteasome for Effective Assembly of Viroplasms R. Contin et al. Journal of Virology, 2011;85(6):2781-2792

 Proteases/HSP90/HSP70 6XUZKGYUSK.96

Proteasome

S1013 Bortezomib Synonyms: Velcade, MG-341, PS-341 Size Price

The dipeptide boronic acid inhibitor bortezomib effectively inhibits proteasome activity (Ki-0.6 nM) but has little 10mg O OH H affinity for other proteases (e.g., for chymotrypsin, Ki=320 nM, and for thrombin, Ki=13,000 nM). The level of N N B N OH H apoptosis was 80% to 90% in cells treated with bortezomib plus SN-38, vs. 10% with either agent alone. O N Feed S1013 Bortezomib

HER/HER2-PI3K-Akt-NF-jB signaling regulates sPLA2-IIa promoter activity. (A) Human sPLA2-IIa promoter sequence (accession numberNC_000001). The C/EBP-binding site in the core promoter region is indicated by bold letter. The consensus sequence of the NF-jB site located at _782 bp was indicated by underline. Most NF-jB sites appear "€¶€]Ƃ\!~~?ÆZ‚€Z\ Z!$|^M~ƒŒ\~„|^ƒŒ\~„;}|~ƒ *„Œ;}}|‘""ƒŒ€|"$]ƒ$|"'ƒZ Gefitinib (20 lM), Lapatinib (20 lM), CI-1033 (8 lM), LY294002(20 lM) and Bortezomib (20 lM) without or with EGF (100 ng/ml) for 24 h. Luciferase assay was performed according to a standard protocol with Renilla luciferase as an internal control. Data are presented as the mean (±SD) of duplicate values of a representative experiment that was independently repeated for five times. Data from Carcinogenesis vol.31 no.11 pp.1948-1955,2010 using our products.

S1380 Lopinavir Synonyms: ABT-378 Size Price

HN O N Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. As a component of combination therapy 10mg O to treat HIV/AIDS. Inhibition of HIV-1 protease prevents cleavage of the viral polyprotein precursor and results HN in the release of immature, noninfectious virions. HO ] O O N H 100mg

<];• Synonyms: Reyataz, BMS-232632 Size Price

N Atazanavir is an antiretroviral drug of the protease inhibitor class. Like other antiretrovirals, it is used to treat ] infection of human HIV. Atazanavir is distinguished from other PIs in that it can be given once-daily and has O OH O H H 10mg N N N O lesser effects on the patient’s lipid profile. Like other protease inhibitors, it is used only in combination with O N N H H O O other HIV medications. ]

S2180 MLN 2238 Size Price Cl O OH H 'Œ\?‘*]*"}~]"€*?$< 10mg N B N OH nM. Proteasome activity was significantly inhibited in both blood and tumor following a single dose of H MLN2238 administered IV at 14 mg/kg or SC at 4 mg/kg. It is active in preclinical models of lymphoma, and O ]" that MLN2238 has antitumor activity in a model of lymphoma that is refractory to bortezomib treatment. Cl 200mg S2181 MLN9708 Size Price

O O OH MLN9708 is an orally bioavailable second generation proteasome inhibitor with potential antineoplastic 10mg Cl O O H activity. MLN9708 rapidly hydrolyzes to MLN2238, the biologically active form. It has a shorter proteasome N B N O dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared ]" H OH O O with bortezomib. MLN9708 showed a correlation between greater pharmacodynamic responses and 200mg Cl improved antitumor activity. ‘]‚ Synonyms: Norvir, Norvir Softgel Size Price

Ritonavir is an inhibitor of HIV protease used to treat HIV infection and AIDS. More specifically, ritonavir is 10mg H O N €€••Z„<]"?;< N N N ]" HO H (CYP3A4). The drug’s molecular structure inhibits CYP3A4, so a low dose can be used to enhance other O O S S protease inhibitors. This discovery has drastically reduced the adverse effects and improved the efficacy of N O H 100mg N PI’s and HAART.

HSP-70 (Heat shock proteins-70)

"] Synonyms: STA-4783 Size Price

Elesclomol is a small molecule that induces apoptosis via the mitochondrial apoptotic pathway in cancer 10mg O O cells by increasing oxidative stress. It is a pro-apoptotic agent that demonstrates anti-tumor activity against a N N N N broad range of cancer cell types. It promotes apoptosis in Hs294T melanoma cells treated with 100 nmol/L ]" H H S S for six hours by rapidly generating reactive oxygen species and inducing the transcription of Hsp70 and metallothionein. 200mg

 Solutions to Signal Transduction Research **6.96  Proteases/HSP90/HSP70

DPP-4 (Dipeptidyl peptidase-4)

S4002 Sitagliptin phosphate Synonyms: MK-0431, Januvia Size Price

CF3 10mg F N Sitagliptin abolished sDPP-IV effects on splenic CD4+ T-cell migration whereas incretins decreased migration N of lymph node, but not splenic, CD4+ T-cells. Sitagliptin decreases migration of splenic CD4+ T-cells through N N a pathway involving Rac1/VASP, whereas its inhibitory effects on the migration of lymph node CD4+ T-cells ]" NH2 O F *\'^$ F 200mg H3PO4 HSP-90 (Heat shock proteins-90)

S1141 17-AAG Synonyms: Tanespimycin, Geldanamycin Size Price O H N H2C O 17-AAG is a less toxic analogue of the geldanamycin which binds to Hsp90 and alters its function. This agent ] CH N 3 H O displays a 100-fold higher affinity for HSP90 derived from tumor cells compared to HSP90 from normal cells. H3C H H3CO 100mg O 17-AAG binds into the ATP binding pocket in Hsp90 and induces the degradation of proteins that require this H3CO CH3 chaperone for conformational maturation. 17-AAG inhibits Akt activation. H3C OCONH2 200mg

S1142 17-DMAG Synonyms: ;Zš"Z\~"]<] Size Price O H N ] HCl N O 17-DMAG, a watersoluble geldanamycin analog belonging to the class of benzoquinones, is a selective Hsp90 CH N 3 H inhibitor. 17-DMAG binds to the N-terminal domain ATP binding site of Hsp90, inhibiting Hsp90 chaperone O H3C H 100mg H3CO activity. 17-DMAG demonstrates greater potency and water solubility than other geldanamycin analogs such O H3CO CH3 ;;|}]"€]??'* ';;;ƒ$

H3C 200mg OCONH2 S1498 NVP-BEP800 Synonyms: †‚‘]# Size Price

Cl O 10mg N \†„^„‘""Z*€Z}~]"*"$"]‘/"$""#)'$} to the NH -terminal ATP-binding pocket of Hsp90. Given the mechanism of action, preclinical activity profile, Cl 2 tolerability, and pharmaceutical properties, NVP-BEP800 is an exciting new oral Hsp90 inhibitor warranting ]" HN N further development. S H2N N O 200mg

]^}}^" Synonyms: CNF2024 Size Price Cl BIIB021 is a novel fully synthetic inhibitor of Hsp90. It binds competitively with geldanamycin in the ] N N ATP-binding pocket of Hsp90 (Ki=1.7nM). BIIB021 induced the degradation of Hsp90 client proteins (including H N N N 2 N HER-2, AKT, and Raf-1) and up-regulated expression of the heat shock proteins Hsp70 and Hsp27. BIIB021 10mg |ZZ€ƒ|}~]"Š ] O #"']"'ƒ$ S2204 Atazanavir sulfate Synonyms: ^'?#?"]Z~„?]<Z‚•Z› Size Price

10mg 1(: N ;•€*[}†~]"~_"*$#]$?'_]' in cell culture. Atazanavir is generally more potent than the five currently approved HIV-1 Prt inhibitors. O OH O H H ;•*€]] ]" N N N O O N N H H Z~]"*–<'$ O O 200mg H2SO4 S1069 NVP-AUY922 Synonyms: ;Ÿ_Z†‚]_# Size Price

HO \†„;Ÿ_[„_"[„_"}~]"|ƒ€*? ] OH and 21 nM, respectively. In a representative panel of human tumor cell lines, NVP-AUY922 inhibited cell O *“}]"|]"’ƒ€ 10mg N *$?]"'$ N O NH ] O

Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  „ŠÇ‘?]‘‘]‘ Proteases/HSP90/HSP70 'SOTUVKVZOJGYK.)<VXUZKGYK

Aminopeptidase

]~[‚_ Synonyms: Tosedostat Size Price

}~]"*""Z]"Z"Z”"""Z”]"""Z”""""”?"""" ] O nM for LAP, PuSA, aminopeptidase N, aminopeptidase B, PILSAP, LTA4 hydrolase and MetAP2, O N respectively. It has demonstrated anti-tumour activity in a number of models of cancer, both as a single 10mg H O O HO agent and in synergy with cytotoxic agents such as carboplatin and paclitaxel. HN ]" OH ]_Ÿ– Synonyms: Bestatin Size Price OH O H Ÿ–^}~]"*""*]#$; 10mg N OH –*]#–~ ?Z€ expression of CD13 was not observed. Other aminopeptidase inhibitors such as amastatin A, arphamenine ] NH2 O ^!']**$ ]" HCV protease

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O ^'_""]*Z[~†\];$\]; 10mg NH H O O N N N *[~†–$^'_""]– N N N O O ]" H HN |~]"]"ƒ|~]"_ƒ$^'_""]€€ O HCV RNA (-3.6 logs after 48 hours from a single 100 mg) dosefollowing a single dose in patients chronically infected with HCV genotype 1. 200mg

S1183 Danoprevir Synonyms: ‚Z}'\_Z‚š]_"]_ Size Price

O F N O Danoprevir is a highly potent, orally absorbed inhibitor of the NS3/4A protease for treating chronic HCV 10mg O H N S infections. In biochemical assays using HCV NS3/4A protease domains derived from genotypes 1b, 1a, 2, or N N O O H ]" O O ?Z~]"€* ®?""'Z<""'Z<""'$<'Z$Ÿ*~„<]" O N H }'\_•€~„<]"*$ 200mg

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O H N [~†}~]"*®"$3'$}– ] O HN O H O O treatment for hepatitis C. Specifically, it inhibits the hepatitis C virus NS3.4A serine protease. H N 10mg N N N H O N H ] S1480 VX-222 Synonyms: VCH222 Size Price

O †°€€*[~†\]^* 10mg S OH O *~€*$![~† N ]" agents furthest along in the development pipeline, HCV polymerase - an enzyme responsible for copying viral $†°€[~†\]^ with potent in vitro activity. 200mg OH

 Solutions to Signal Transduction Research ![\

Notch signaling has a critical role in regulating cell to cell communication during embryogenesis, cellular proliferation, differentiation, and apoptosis. Notch signaling is also critical for normal hematopoiesis, breast develop- ment, colorectal epithelial maturation, immune regulation, and neural stem €$ * M € communication between adjacent cells. The extra cellular region of the notch receptor contains numerous epidermal growth factor like domains that mediate interactions with notch ligands. Affinity between the notch ligand and receptor depends on the extent of epidermal growth factor domain fucosylation by the Fringe proteins.

The Hh signaling pathway controls tissue polarity, patterning maintenance, and stem cell maintenance during embryonic development. Hyperactivation of this pathway, by either mutation or deregulation, has recently been recog- nized to cause tumorigenesis in a wide variety of tissues. Hh pathway involvement has been observed in other types of nonmutation driven, para- crine deregulation of signaling. ! * _   ligands for the Frizzled transmembrane receptor. During embryogenesis, wnt proteins direct cell fate determination at various stages of development and their signaling acts to regulate the development of a variety of organ systems including cardiovascular, central nervous system, renal, and lung. In adults, wnt signaling has a key role in the regulation of tissue selfrenewal, particularly in intestinal crypts, hair follicles, and bone growth plates.

Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Naoko Takebe et al. Nat Rev Clin Oncol, 2011(8):97-106

 Wnt/Hedgehog/Notch .KJMKNUM=TZŝYKIXKZGYK

Hedgehog

S1146 Cyclopamine Synonyms: 11-deoxojervine Size Price

H ] H OH O Cyclopamine inhibits the hedgehog signaling pathway by influencing the balance between the active and inactive forms of the Smoothened protein. It antagonizes Smo activity by binding to its heptahelical bundle. N 10mg H Thus, it can block pathway activation resulting in any of the two upstream events of Smo. H H H ]

S1082 GDC-0449 Synonyms: HhAntag691, Vismodegib Size Price

Cl O Cl ~"<<_*}~]"*? ] N nM. It targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface N 10mg H receptors PTCH and/or SMO and suppressing Hedgehog signaling. It inhibits the growth of primary S pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation in vitro and has recently ]" O O entered the clinic. Wnt (combination of Wg (wingless) and Int)

S1180 XAV-939 Size Price

HO °;†_?_€!* 10mg –•}~]"*<'**\\Z N $}€•–Z ] CF3 of the destruction complex and stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 S N and tankyrase 2. ]"

  Feed S1280 XAV-939   Cells plated at 2 x 10E4 in 24 multiwell with DMEM 10% FBS preconditioning 24 hrs (pretreatment withour wnt) switch medium  *’[Ç!\""   Data from Dr Marco Quarta , Stanford University - School of Medicine    &75/ :17 X0 X0 X0

S1262 BMS-708163 Size Price

CF3 10mg O O ^'"‘#?|}ƒ|}~]" "$?'ƒ$^'"‘#?}~]" H N S Cl 2 N * ;„„  * "$? 'Z * }_]?Z  } |] 'ƒ$ ]" O ^'"‘#?Z_"**;„„\Z}~]"*]‘'*\$ N F O N 200mg ]]‚š<__"_ Synonyms: RO-4929097 Size Price

F F H F ‚š<__"_Z€}~]"*<'$} 10mg O H N N F to GS and blocks activation of Notch receptors. RO4929097 inhibits Notch processing in tumor cells. This HN F ]" O O leads to reduced expression of the Notch transcriptional target gene Hes 1. RO4929097 does not block tumor cell proliferation or induce apoptosis but instead produces a less transformed, flattened, slower-growing phenotype. 200mg

]_< Synonyms: Œ<]"?_ Size Price

N S }~]"*]'$**;„„$ 10mg N Research on laboratory rats suggest that the soluble form of this peptide is a causative agent in the N NH 2 *;•R$•Z|ƒ ]" F F responsible for APP proteolysis. 200mg

 Solutions to Signal Transduction Research Jak/Stat

The current model of Jak-Stat signaling holds that cytokine receptor engagement activates the associated Jak combination, which in turn phos- phorylates the receptor cytoplasmic domain to allow recruitment of a Stat, which in turn is phosphorylated, dimerizes and moves to the nucleus to bind specific sequences in the genome and activate gene expression. Cytoplas- mic domains of cytokine receptors associate with Jaks via Jak binding sites located close to the membrane. Regardless of the when and where cytokine receptors and Jaks associate, their close apposition at the membrane is required to stimulate the kinase activity of the Jak following cytokine binding. At this stage in the activation of the pathway, we understand next to nothing about the structural basis of the Jak-receptor interaction, how receptor intra- cellular domains reorient upon cytokine binding and physically contact the Jak to receive the phosphorylation modification.

Jak-mediated phosphorylation of the receptor creates binding sites for the Src homology 2 (SH2) domains of the Stats. Stat recruitment is followed by tyrosine, and in some cases, serine phosphorylation on key residues (by the Jaks and other closely associated kinases) that leads to transit into the nucleus. This brief summary of the activation of the Jak-Stat pathway omits numerous unresolved details: the Stat monomer to dimer transition has been questioned, as has the role of phosphorylation in dimerization and nuclear transit. Furthermore, it is unclear how many configurations of Stat homo- and heterocomplexes are present in cells before, during, and after cytokine stimulation.

The JAK-STAT Signaling Pathway: Input and Output Integration. Peter J. Murray. J Immunol, 2007(178):2623-2629.

 Jak/Stat 9ZGZ0GQ

Stat (Signal transducer and activator of transcription)

‘]~ Size Price O O ~–€;?}~]"*<$#)'$} 10mg antibacterial and anti-inflammatory activity and acts as an antidiabetes and antiobesity agent via activation of O AMPK. It also improves cognitive impairment in Alzheimer’s disease transgenic mice by inhibition of ] }~]"*<$"_)'€; peptide generation. ]"

]]?" Synonyms: \~<‘]_ Size Price OH

O ?"??–*? \;|}~]" ‘#/??)'ƒ 10mg HN activities. Furthermore, S31-201 inhibits growth and induces apoptosis preferentially in tumor cells that contain O OH persistently activated Stat3. S31-201 inhibits the expression of the Stat3-regulated genes encoding cyclin D1, ]" S O O BcI-xL, and survivin and inhibits the growth of human breast tumors in vivo. O 200mg Jak (Janus-family tyrosine kinase)

#;› <‘" Size Price Cl H N 10mg HN N ;› <‘"¦;}~]"*"$#'$}*¦ *?€€$;› <‘"* NN F ]" N ]}~]"*<#'Œ¦Z*] HN Œ¦?ZŒ¦ZŒ)';› <‘"$ N 200mg

]""~„#_"]]" Synonyms: Tasocitinib Size Price

The somatic activating JAK2 V617F is detectable in most patients with polycythemia vera. Enzymatic assays 10mg N N CN ¦;¦;"""*~„#_"Z]]"Z O respectively, when compared with JAK3. JAK2V617F-bearing cells were almost 10-fold more sensitive to ] N ~„#_"Z]]"¦;!Z}~]"*"$])'$)'Z$ N N ]" H _Œ‘<]<< Size Price

O N Œ‘<]<<€€¦;}~]"*#‘'$} 10mg

N NH N tests using Ba/F3 cells expressing either wild type or V617F mutant JAK2, it potently inhibited the JAK2 N ]" N N †#;]<*¶€}Œ? H ¦;;]|}~]" "$"]]3'*¦;†#$$#3'*!¦;ƒ$ F 200mg Cl <;›_#" Size Price F H N N ;›_#"€¦;}~]"*?'"$<]'Z 10mg NH N $;›_#"Z€;Z;€;Z;Z N HN }~]"*€"$)'$;›_#"*^–Œ'' ]" accumulation of cAMP response element-binding protein bound to the Bcl-xL promoter as measured by chromatin immunoprecipitation assay. 200mg

F

S1143 AG-490 Synonyms: Tyrphostin AG490 Page 4

S1134 AT9283 Page 11

 Solutions to Signal Transduction Research Ca/cAMP/Lipid

All PKC isoforms share a highly conserved carboxy-terminal kinase domain that is linked by a hinge region to a more divergent amino- €$!Z„~€ pseudosubstrate sequence that is present in the regulatory domain, which occupies the substrate binding pocket in the otherwise func- tional kinase domain. PKC is activated when second messengers and/or allosteric effectors bind to its regulatory domain, typically at the plasma membrane. This disrupts the docking of the regulatory kinase domain, which displaces the bound pseudosubstrate region from the active site, allowing the activation of PKC.

The modular nature of this family-PKCs have a conserved kinase domain coupled to a series of differentially activated regulatory domains - allows PKC activity to be deployed with spatial and temporal specificity. It also allows PKC activity to be directed by multiple inputs, including localized (membrane limited) second messenger production and interaction with membrane-anchored small G proteins, scaffolds and accessory proteins. As a result the PKC family is centrally involved in the spatial control of signal transduction in cells.

PKC and the control of localized signal dynamics. Carine Rosse et al. Nat Rev Mol Cell Bio, 2010(11):103-112.

 Ca/cAMP/Lipid 61)

PKC (Protein kinase C)

S1292 Chelerythrine Chloride Size Price

] O Chelerythrine is a benzophenanthridine alkaloid extracted from the plant Greater celandine (Chelidonium ¬€ƒ$}ZZ„~|}~]" ##"'ƒ$}* O 10mg N+Me biological activities, including antiplatelet, anti-inflammatory, antibacterial and antitumor effects. O - O Cl ]"

"]]•€ Synonyms: Œ?#] Size Price

O NH 10mg N •€€''$}~]"*"$#$# O )'$•€**€€Z€€* N of cultured tumor cells. ]"

N 100mg N

S2391 Quercetine Synonyms: Sophoretin, Meletin, Quercetine 1(: Page 12

 Solutions to Signal Transduction Research Neuro Signaling Pathway

SNAPR (Peptides) 103 NKR (Peptides) 103 BDKR/KOR (Peptides) 103 TRH receptor (Peptides) 104 CGRP (Inhibitors) 78 COX (Inhibitors) 78 GABA transporter (Inhibitors) 98 "'"%* 72 mGluR2/mGluR3(Inhibitors) 83 Serotonin Reuptake(Inhibitors) 93

 Neuro Signaling Pathway )-86)5>

CGRP (Calcitonin gene-related peptide)

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O 10mg O MK3207 hydrochloride is a potent and orally bioavailable CGRP receptor antagonist. In vitro, it is a potent HN O NH N antagonist of the human and rhesus CGRP receptors (Ki = 0.024 nM). In common with other CGRP receptor N N ]" H antagonists MK-3207 displays lower affinity for CGRP receptors from other species including canine and rodent. 200mg F F COX

S1634 Acetaminophen Synonyms: Paracetamol, Tylenol Size Price

OH ;*~š°#„}~]"*?"$? 10mg O "3'Z$\*–*„[ prostacyclin formation by aortic endothelial cells. This elevated activity was efficiently inhibited by pharmacologically ]" N *|}~]"–"3'*#„ƒ* H radical scavengers. 200mg S1903 Diclofenac sodium Synonyms: Voltaren, Solaraze, Ecofenac, Benfofen Size Price

*~š°}~]"*#""'*~š°Z$ 10mg }€~š°}~]"€*"$_$$]"3'Z$}€ Cl Cl ] Na+ primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is inhibition of HN- prostaglandin synthesis by inhibition of COX, and it appears to inhibit DNA synthesis. O ]" O S1638 Ibuprofen Synonyms: Genpril, Brufen, Nurofen, Motrin, Ibren, Ibuprohm Size Price

}€*~š°}~]"*?$?–"-4 M. It is known to have an antiplatelet 10mg OH effect, though it is relatively mild and short-lived when compared with that of aspirin or other better-known antiplatelet drugs. Ibuprofen, indomethacin, and meclofenamate were potent inhibitors of the microsomal ]" O –**€}~]"*?$?&"-4'Z$_&"]'Z<$&"-6 M, respectively. 200mg

#<]* Synonyms: Orudis, Oruvail, Ketoflam, Orudis KT Size Price

O *\;} –}~]"*"$])'$??)'*€~š° 10mg OH and COX-2, respectively. It is used for its antipyretic, analgesic, and anti-inflammatory properties by inhibiting COX-1 and COX-2 enzymes reversibly. Robenacoxib was COX-2 selective, diclofenac and ]" O meloxicam were only weakly COX-2 preferential, and ketoprofen was COX-1 selective. 200mg

S1626 Naproxen Sodium Synonyms: Anaprox, Miranax, Naprelan, Naposin, Antalgin Size Price

\–€|;ƒ–|~š°ƒ}~]"*‘$b/"$?$ 10mg ONa It displays anti-inflammatory, antipyretic and analgesic effects and has a neuroprotective role against colchicine-induced cognitive impairment and oxidative stress. ]" O O 200mg

S1713 Piroxicam Synonyms: Feldene, Roxam Size Price

O OH „–~š°}~]"*#'$}*€ 10mg N N used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; H and acts as an analgesic, especially where there is an inflammatory component. ] N S O O ]" GABA Page 98

Page 72 mGluR2/mGluR3 Page 83

Serotonin Reuptake Page 93

 Solutions to Signal Transduction Research

Transforming growth factor (TGF) is the prototype of a family of secreted polypeptide growth factors. To date, up to 33 TGFrelated genes have been identified in mammalian genomes as the result of genome sequencing proj- ects; these include bone morphogenic proteins, activin/inhibin, growth and differentiation factors, nodal, and anti-Müllerian hormone. These cytokines play very important roles during development, as well as in normal physi- ological and disease processes, by regulating a wide array of cellular processes, such as cell growth, differentiation, migration, apoptosis, and extracellular matrix production. However, in a different cellular context, TGF can also promote tumor growth because it is able to induce changes in tran- scriptional activities that re-program epithelial cells into mesenchymal cells, thereby facilitating tumor metastasis and invasion.

Over a decade ago, genetic studies in worms and fruitflies uncovered a group of genes, later dubbed as Smads, which appear to play a crucial role in mediating the intracellular responses to TGF and/or its related factors. Subsequent biochemical characterization demonstrated that Smads are transcription factors that constantly shuttle between the cytoplasm and the €€$ ! Z € * changes that allow direct binding of Smads and their phosphorylation by the kinase activities of the cytoplasmic domains of the type I receptors. This results in the accumulation of Smads in the nucleus to regulate target gene transcription. The identification of Smads elated the field of TGF signaling, but it also instigated a perplexing dilemma in terms of reconciling the diverse functions of the TGF family with the simplicity of the Smad signaling model.

Non-Smad pathways in TGF signaling. Ying E Zhang. Cell Res, 2009(19):128–139.

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 Solutions to Signal Transduction Research GPCR

GPCRs (Guanine Nucleotide Binding–Protein Coupled Receptors) comprise large and diverse gene families in fungi, plants, and the animal kingdom. Also termed serpentine receptors, GPCRs are polytopic membrane proteins that share a common structure with seven transmembrane segments, but sequence similarity is minimal among the most distant GPCRs. Their principal function is to transmit information about the extracellular environment to the interior of the cell, and they do this by interacting with the G-proteins. GPCRs recognize a variety of ligands and stimuli including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases, biogenic amines, nucleosides, lipids, growth factors, odorant molecules and light. These receptors affect the generation of small molecules that act as intracellular mediators or second messengers, and can regulate a highly interconnected network of biochemical routes. The intracellular signaling pathways activated by GPCR signaling include cAMP/ PKA pathway, Ca2+/PKC pathway, Ca2+/NFAT pathway, PLC pathway, PTK pathway, PKC/MEK pathway, p43/p44MAPK pathway, p38 MAP pathway, PI3K pathway, NO-cGMP pathway, Rho pathway, NF-KappaB pathway and JAK/ STAT pathway.

G protein-coupled receptor microarrays for drug discovery. Fang Y et al. Drug Discov Today, 2003;8(16):755-761.

 GPCR

Vasopressin Receptor

S1990 Capsaicin Synonyms: Qutenza, Vanilloid Size Price

HO Capsaicin is an active component of chili peppers. Capsaicin, as a member of the vanilloid family, binds to a 100mg H N receptor called the vanilloid receptor subtype 1. By binding to the VR1 receptor, the capsaicin molecule O produces the same sensation that excessive heat or abrasive damage would cause, explaining why the 200mg O spiciness of capsaicin is described as a burning sensation. 500mg

Angiotensin Receptor

S1578 Candesartan Synonyms: Atacand, Blopress, Amias, Ratacand Size Price O OH HN N Candesartan is an angiotensin II receptor antagonist with an IC50 of 15 μg/kg. It reduced the risk of developing 10mg N N hypertension by nearly two-thirds during this period. In the last two years of the study, all participants were N switched to placebo. By the end of the study, candesartan had significantly reduced the risk of hypertension, 25mg N O by more than 15%. 50mg

S1587 Olmesartan Synonyms: Benicar, Olmetec Size Price

N HN N N Olmesartan is an angiotensin II receptor antagonist with an IC50 of 7.7 nM. Olmesartan works by blocking the 10mg O binding of angiotensin II to the AT1 receptors in vascular muscle; it is therefore independent of angiotensin II O O N O synthesis pathways, unlike ACE inhibitors. By blocking binding rather than synthesis of angiotensin II, 25mg O N olmesartan inhibits the negative regulatory feedback on renin secretion. HO 50mg S1539 Tasosartan Synonyms: DB01349 Size Price

H N Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an N N 10mg N alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly

N developed nonpeptide AT1 receptor blocker. IC50s were determined from log-dose response curves by 25mg N N nonlinear regression analysis. O 100mg

S1894 Valsartan Synonyms: Diovan Size Price

O OH HN N Valsartan is an angiotensin II receptor antagonist with IC50 of ranging from 39.5 to116 μM. By blocking the 10mg N N N action of angiotensin, valsartan dilates blood vessels and reduces blood pressure. In the Value trial, the H O angiotensin II receptor blocker valsartan produced a statistically significant 19% (p=0.02) relative increase in 50mg the prespecified secondary end point of myocardial infarction compared with amlodipine. 100mg

CB1 Receptor

S1595 AM 281 Size Price

O AM 281 is a potent, selective CB1 cannabinoid receptor antagonist with an Ki of 12 nM and 4200 nM for CB1 NH 10mg N and CB2 receptors respectively. It increases locomotor activity following systemic administration in vivo. N N 50mg I O Cl 100mg

Cl

 Solutions to Signal Transduction Research ŜXKIKVZUX9SUUZNKTKJ GPCR

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S1549 Nebivolol HCl Synonyms: Bystolic, R-67145 Size Price OH OH H O N O \}~]"*<$]3'$}–** 1mg H H used in treatment of hypertension. Nebivolol was compared with DETA-NO and SNAP, two nitric oxide donor F F agents, and DFMO, a known inhibitor of ODC. All four test agents inhibited RASMC proliferation in a 5mg concentration-dependent manner, with nebivolol being the most potent (IC(50) = 4.5 microM). HCl 10mg

S1206 Bisoprolol Fumarate Synonyms: Zebeta Size Price

^  € |ƒ$ ' *Z  25mg OH adrenergic receptor blocker. Bisoprolol can be used to treat cardiovascular diseases such as hypertension, NH O coronary heart disease, arrhythmias, is chemic heart diseases and treatment of myocardial infarction after the 100mg O O acute event. OH OH 200mg O O S2509 Sotalol HCl Synonyms: Betapace, Betapace AF, Berlex Laboratories, Sotalex Size Price

HO Sotalol(Betapace) is a non-selective beta blocker and a potassium channel blocker with an IC50 of 43 μM. 50mg NH Sotalol definitely distinctly located binding site to interfere with K+ permeation; both enantiomers associated O HN S with a rate close to 5×105 /mol/ sec with the open pore thereby flicker-blocking cardiac K+/ATP channels. 100mg O 200mg HCl Smoothened

S2151 LDE225 Synonyms: NVP-LDE225 Size Price

F3CO LDE225(NVP-LDE225) is a novel and specific, orally bioavailable Smo inhibitor with an IC50 of 11 nM. It has 10mg been shown to potentially inhibit Hh-and Smo-dependent proliferation in vivo. It also induced the regression of *}~]"*®]"$])$ 25mg N HN N O 50mg

O mGluR2/mGluR3

S6001 LY2140023 Synonyms: LY404039 Size Price

O H O LY404039 is a selective metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3 agonist with 10mg HOOC S Ki of 149 and 92nM for mGlu2 and mGlu3, respectively.Functional activity of LY404039 at group II and group III mGlu receptors is measured by the inhibition of forskolin-stimulated cAMP formation. It is nanomolar potent 50mg H agonists at human mGlu2 and mGlu3 receptors, as indicated by the inhibition of forskolin-stimulated cAMP H COOH formation (LY404039: mGlu2, EC50 =23 nM; mGlu3, EC50 = 48 nM). 200mg NH2

Feed S600 LY2140023 Top:The glutamate agonist LY404,039 inhibited the 3 binding of 2 nM [ H]domperidone on dopamine D2Long receptors (in CHO cells). The inhibition occurred in two concentration phases of LY404,039, with 15.5% inhibition for the high-affinity phase. 120 mM NaCl present. Data points are mean values (with SE; n = 3). The inhibition of 15.5% occurred at D2High receptors, all of which were converted to low-affinity D2Low receptors in the presence of GN (200 μM guanylylimidodiphosphate). The dissociation constant, High Ki , of LY404,039 was 8.2 ± 1 nM. Nonspecific binding was defined in the presence of 10 μM S-sulpiride. Bottom: LY404,039 35 stimulated the incorporation of [ ³„ Long receptors with 50% incorporation occurring at 80 ± 15 nM. The maximum amount of stimulation was 43% of that caused by 10 μM dopamine. The stimulation was blocked by 10 μM S-sulpiride. Data points are means ± SE (n = 3). Data from SYNAPSE 63:935–939 (2009), using our product.

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Historically, the first important role ascribed to plasma membrane ion chan- nels, over 60 years ago, was their participation in cellular electrogenesis and electrical excitability. However, numerous subsequent studies have firmly established the contribution of ion channels to virtually all basic cellular behaviors, including such crucial ones for maintaining tissue homeostasis as proliferation, differentiation, and apoptosis. The major mechanisms via which ion channels contribute to these crucial processes include: providing the influx of essential signaling ions, regulating cell volume, and maintaining membrane potential. Malignant transformation of cells resulting from enhanced proliferation, aberrant differentiation, and impaired ability to die is the prime reason for abnormal tissue growth, which can eventually turn into uncontrolled expansion and invasion, characteristic of cancer. Such trans- formation is often accompanied by changes in ion channel expression and, consequently, by abnormal progression of the cellular responses with which they are involved.

Ion channels in death and differentiation of prostate cancer cells. N Prevarskaya et al. Cell Death Differ, 2007(14):1295–1304;

 ),:8)GRIO[SINGTTKR Ion Channel

CFTR

S1144 VX-770 Size Price H N VX-770 is a CFTR potentiator with an IC50 of 43 ± 38 nM. In recombinant cells VX-770 increased CFTR 10mg H channel open probability in both the F508del processing mutation and the G551D gating mutation. VX-770 N also increased Cl- secretion. Furthermore, VX-770 reduced excessive Na+ and fluid absorption to prevent 50mg O O dehydration of the apical surface and increased cilia beating in these epithelial cultures. 200mg OH Calcium channel

S1885 Felodipine Synonyms: Plendil, Renedil, Feloday Size Price Cl Felodipine is a calcium channel blocker with an IC50 of 3 μM for the formyl-Met-Leu-Phe-induced cytosolic 10mg Cl O O calcium increase. It is a drug used to control hypertension. Grapefruit juice contains bergamottin which is found to have an inhibiting effect over this enzyme and as a result the bioavailability of the drug increases, 25mg O O raising the risk for abnormal side effects. N 50mg H S1662 Isradipine Synonyms: DynaCirc, Prescal, PN-200-110, Clivoten, Esradin Size Price N O }€}~]"*?

O Amlodipine besylate is a long-acting dihydropyridine calcium channel blocker. Amlodipine is a calcium channel 25mg HN O blocking agent. The decrease in intracellular calcium inhibits the contractile processes of the myocardial O H N 50mg 2 O smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the S O O HO myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure and decreased Cl O 100mg afterload. S1905 Amlodipine Synonyms: Istin, Norvasc Size Price O Amlodipine is a long-acting calcium channel blocker with an IC50 of 1.9 nM used as an anti-hypertensive and 10mg HN O O in the treatment of angina. Amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing total H2N peripheral resistance and hence reducing blood pressure; in angina it increases blood flow to the heart 25mg O O muscle. Cl 50mg

S1747 Nimodipine Synonyms: Nimotop Size Price H N Nimodipine inhibits the transmembrane influx of calcium ions in response to depolarization in smooth muscle 200mg O O O cells, thereby inhibiting vascular smooth muscle contraction and inducing vasodilatation. Nimodipine has a O O greater effect on cerebral arteries than on peripheral smooth muscle cells and myocardial cells, probably 500mg because this agent can cross the blood brain barrier due to its lipophilic nature. NO2 1g

S1748 Nisoldipine Synonyms: Sular, Zadipina, Bay k 5552, Baymycard Size Price H N Nisoldipine is a calcium channel blocker. It works by affecting the movement of calcium into the cells of the 25mg O O heart and blood vessels. As a result, it relaxes blood vessels and increases the supply of blood and oxygen to O O the heart while reducing its workload. 50mg

NO2 100mg

S2491 Nitrendipine Size Price O- N+ Nitrendipine is a dihydropyridine calcium channel blocker with an IC50 of 95 nM. Nitrendipine and BRL 38227 10mg O cause concentration-related inhibitions of the inositol phosphate response to histamine (100 μM). Similar O O maximal inhibitions were caused by each agent (55-58%). Inhibitory effect of BRL 38227 was reduced in 25mg O O potency (IC50 = 5.5 μM), but not magnitude, in the presence of glibenclamide (0.5 μM). 50mg N H

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S1293 Cilnidipine Synonyms: FRC 8653 Size Price H N Cilnidipine is a calcium channel blocker. It is a dual blocker of L-type voltage-gated calcium channels in 20mg O O O vascular smooth muscle and N-type calcium channels in sympathetic nerve terminals that supply blood 50mg O O vessels.

NO2 500mg Proton pump

S1743 Esomeprazole magnesium Synonyms: Nexium Size Price O

N Esomeprazole magnesium is a proton pump inhibitor which reduces gastric acid secretion through inhibition 10mg O N- S of H+/K+-ATPase in gastric parietal cells. By inhibiting the functioning of this enzyme, the drug prevents ++ N O Mg O N formation of gastric acid. 25mg S N- O N 50mg

O S1354 Lansoprazole Synonyms: Prevacid, Prevacid NapraPAC, Prevacid SoluTab Size Price

Lansoprazole is a proton-pump inhibitor which prevents the stomach from producing gastric acid.It is used to 1g N F F treat duodenal and gastric ulcers, erosive esophagitis, and gastroesophageal reflux diseas. Lansoprazole is O N S F also used to treat Zollinger-Ellison syndrome, which is a condition where the stomach produces too much acid. 5g H O N 10g

S1389 Omeprazole Synonyms: Losec, Omesec, Prilosec, Zegerid Size Price H N O Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), 500mg S N gastroesophageal reflux disease (GORD/GERD), laryngopharyngeal reflux, and Zollinger-Ellison syndrome. O N 1g

O 5g

 Solutions to Signal Transduction Research Cytochrome P450

The cytochromes P-450 (CYP) are a superfamily of heme-thiolate enzymes, some of which play major roles in the metabolism of drugs and other xenobi- otics, although endogenous compounds can also be their substrates. In humans and other mammalian species, CYP1, CYP2 and CYP3 families are primarily associated with the Phase 1 metabolism of exogenous compounds. Over 90% of all drug metabolism in man is P-450-mediated

The cytochromes P450 (CYPs) are key enzymes in cancer formation and cancer treatment. They mediate the metabolic activation of numerous precar- cinogens and participate in the inactivation and activation of anticancer drugs. Since all CYPs that metabolize xenobiotics are polymorphic, much emphasis has been put on the investigation of a relationship between the distribution of specific variant CYP alleles and risk for different types of cancer, but a consistent view does not yet exist.

Cytochrome P450 pharmacogenetics and cancer. C Rodriguez-Antona et al. Oncogene, 2006(25):1679–1691

 Cytochrome P450 GJKSKZN_RGYK

14a-demethylase

S2135 Cytochrome P450 14a-demethylase inhibitor 1a Size Price

~„<]"<*€*\€• OH 10mg N MIC80 of 3.9 ng/ml against Candida albicans and Microsporum gypseum. It shows 128 times higher activity N N than that of fluconazole against Candida albicans and also shows higher activity than that of the other positive 50mg N F controls. 200mg F S2136 Cytochrome P450 14a-demethylase inhibitor 1b Size Price

F OH Cytochrome P450 14a-demethylase inhibitor 1b exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows 128 times higher activity than that of fluconazole against 50mg N F Candida albicans and also shows higher activity than that of the other positive controls. Its MIC80 against Candida parapsilosis and Candida Krusei is 15.6 ng/ml. 200mg F S1123 Abiraterone Synonyms: CB-7598, CB7598 Size Price

N Abiraterone is a steroidal CYP17 inhibitor. In preclinical studies, Abiraterone has demonstrated the ability to 10mg selectively inhibit the target enzyme (IC50 4 nM for hydroxylase), resulting in nhibition of testosterone H production in both the adrenals and the testes. 50mg

H H 200mg HO S2137 Cytochrome P450 14a-demethylase inhibitor 1c Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1c exhibits higher activity against nearly all fungi tested except 10mg N F N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F N MIC80 against Candida parapsilosis and Candida Krusei is 62.5 ng/ml. 50mg 200mg F S2138 Cytochrome P450 14a-demethylase inhibitor 1d Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1d exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F MIC80 against Candida parapsilosis, Candida Krusei , Cryptococcus neoformans and Candida tropicalis is 50mg N F 62.5 ng/ml. 200mg F

S2139 Cytochrome P450 14a-demethylase inhibitor 1e Size Price

Cl OH Cytochrome P450 14a-demethylase inhibitor 1e exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F N MIC80 against Candida parapsilosis, Candida Krusei and Microsporum gypseum is 62.5 ng/ml. 50mg 200mg F S2140 Cytochrome P450 14a-demethylase inhibitor 1f Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1f exhibits higher activity against nearly all fungi tested except 10mg N Cl N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F N MIC80 against Candida tropicalis and Candida Krusei is 62.5 ng/ml. 50mg 200mg F S2141 Cytochrome P450 14a-demethylase inhibitor 1g Size Price

Cytochrome P450 14a-demethylase inhibitor 1g is exhibits higher activity against nearly all fungi tested except 10mg OH N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F MIC80 against Cryptococcus neoformans, Candida parapsilosis and Candida tropicalis and Trichophyton 50mg N Cl rubrum is 0.25 μg/ml. 200mg F

 Solutions to Signal Transduction Research GJKSKZN_RGYK Cytochrome P450

S2142 Cytochrome P450 14a-demethylase inhibitor 1h Size Price

Br Cytochrome P450 14a-demethylase inhibitor 1h exhibits higher activity against nearly all fungi tested except OH 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its N F MIC80 against Cryptococcus neoformans, Candida parapsilosis, Candida Krusei and Trichophyto nrubrum is 50mg 0.25 μg/ml. 200mg F S2143 Cytochrome P450 14a-demethylase inhibitor 1i Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1i exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F N Br MIC80 against Cryptococcus neoformans, Candida parapsilosis, Candida tropicalis, and Trichophyto nrubrum 50mg is 0.25 μg/ml. F 200mg S2144 Cytochrome P450 14a-demethylase inhibitor 1j Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1j exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its N F MIC80 against Candida albicans is 15.6 μg/ml. 25mg 50mg F S2145 Cytochrome P450 14a-demethylase inhibitor 1k Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1k exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F 25mg N MIC80 against Microsporum gypseum is 15.6 μg/ml. 50mg F S2146 Cytochrome P450 14a-demethylase inhibitor 1l Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1L exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its N F 25mg NO2 MIC80 against Microsporum gypseum is 15.6 μg/ml.

F 50mg S2147 Cytochrome P450 14a-demethylase inhibitor 1m Size Price

OH Cytochrome P450 14a-demethylase inhibitor 1m exhibits higher activity against nearly all fungi tested except 10mg N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F N MIC80 against Microsporum gypseum is 62.5 μg/ml. 25mg

F 50mg S2148 Cytochrome P450 14a-demethylase inhibitor 1n Size Price

Cl Cytochrome P450 14a-demethylase inhibitor 1n exhibits higher activity against nearly all fungi tested except 10mg OH N N N Aspergillus fumigates than fluconazole. It shows higher activity than that of the other positive controls. Its F MIC80 against Candida tropicalis and Candida Krusei and is 0.25 μg/ml. 25mg N Cl 50mg F

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Factor Xa ...... 91 S1P Receptor ...... 91 sPLA2 ...... 91 P-glycoprotein ...... 91 Reverse transcriptase ...... 92 Xanthine oxidase ...... 93 Serotonin reuptake ...... 93 Phosphodiesterase ...... 94 Acetylcholinesterase ...... 95 Adrenergic receptor ...... 96 Histamine ...... 97 GABA ...... 98

 ,GIZUX>G968KIKVZUX'MUTOYZY62'6MR_IUVXUZKOT Others

Factor Xa

S1593 Apixaban Synonyms: BMS-562247-01 Size Price

O Apixaban is a direct factor Xa inhibitor with an IC50 of 0.22±0.02 μM. It is a compound being investigated as 10mg

N N an anticoagulant. Apixaban has similar affinity for human and rabbit factor Xa (FXa). Oxidative metabolism of H N O 2 [14C] apixaban by liver microsomes was approximately 20 times faster in rabbits than in rats or humans. 50mg O N N 200mg O S1571 BMS-740808 Size Price

F3C OH BMS-740808 is a highly potent, selective, efficacious, and orally bioavailable blood coagulation factor Xa 10mg N N N N *?"'$}*|$&"'%ƒZ|”"""* O over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood 50mg coagulation factor Xa. O NH2 N 200mg

S3002 Rivaroxaban Synonyms: Xarelto, BAY 59-7939 Size Price

Cl Rivaroxaban inhibits clot-associated,free FXa activity, and prothrombinase activity, in addition, it reduces 10mg O S thrombin generation. The activated serine protease FXa plays a central role in the blood coagulation cascade. NH O N N ^;]__?_**€*€°|}~]" "$/"$""$‘/"$"$'Z 50mg O O respectively), but was less potent against purified rat FXa. O 200mg

S1P Receptor Agonist

S5002 FTY720 Synonyms: Fingolimod, Gilenia Page 12 sPLA2

S1110 LY315920 Size Price O H2N LY315920 is a selective inhibitor of human, group IIA, nonpancreatic secretory PLA2. In a chromogenic 10mg O isolated enzyme assay, Varespladib inhibited sPLA2 activity with an IC50 of 9.6 ±1 nM or 7.3 ×10-6 mole N OH 50mg O fraction. The use of Varespladib have a beneficial effect in preventing various inflammatory disease states. O 200mg

P-glycoprotein

S1481 LY335979 Synonyms: Zosuquidar trihydrochloride, RS-33295-198 Size Price

F F LY335979 is a selective Pgp inhibitor with a Ki of 59 nM, and does not modulate MRP-mediated resistance by 10mg MRP1 and MRP2. LY335979 significantly enhanced the survival of mice implanted with Pgp-expressing

N murine leukemia (P388/ADR) when administered in combination with either daunorubicin, doxorubicin or 50mg

N etoposide. LY335979 was without significant effect on the pharmacokinetics of these anticancer agents.

O OH HCl HCl HCl N

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Reverse Transcriptase

S1704 Emtricitabine Synonyms: Emtriva, Coviracil, Truvada, Atripla Size Price

O S  €  }~]" * $ )'$ €  10mg NNO OH inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness. 25mg H2N F 50mg S1398 Stavudine Synonyms: Zerit Size Price

HO Stavudine is a nucleoside analog reverse transcriptase inhibitor active against HIV. Stavudine is an analog of 25mg thymidine. It is phosphorylated by cellular kinases into active triphosphate. Stavudine triphosphate inhibits the N O HIV reverse transcriptase by competing with natural substrate, thymidine triphosphate. It also causes 50mg O O N termination of DNA synthesis by incorporating into it. H 100mg S1400 Tenofovir Disoproxil Fumarate Synonyms: Viread Size Price

O Tenofovir disoproxil fumarate belongs to a class of antiretroviral drugs known as nucleotide analogue reverse NH O 10mg 2 O CO2H O transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in N N O O O HO2C 50mg N P O HIV-infected people. N O O 100mg S1742 Nevirapine Synonyms: Viramune, BI-RG 587 Size Price O NH Nevirapine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV-1 infection and AIDS. 5mg Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class. 10mg N N N 25mg S1401 Tenofovir Synonyms: Viread Size Price

NH2 TENOFOVIR is a drug used to treat human HIV infection. Tenofovir is an antiviral drug called a nucleotide 5mg N N reverse transcriptase inhibitor. Tenofovir may reduce the amount of HIV in the blood and increase the number 20mg N PO3H2 of CD4 cells (T-cells) in the blood. Tenofovir is used in combination with other drugs to treat the HIV virus. N O Tenofovir will not cure or prevent HIV infection or AIDS. 50mg

S1718 Adefovir Dipivoxil Synonyms: Bis-POM PMEA, Preveon, Hepsera Size Price

NH2

N N Adefovir Dipivoxil works by blocking reverse transcriptase, an enzyme that is crucial for the HBV to reproduce 50mg in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral N N O O replication and either evidence of persistent elevations in serum aminotransferases or histologically active 100mg O P O O disease. O O 500mg

O S1702 Didanosine Synonyms: 2',3'-dideoxyinosine, DDI, NSC 612049 Size Price

HO O N }~]"*"$<_)'$}**[}†€ 5mg N combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy. O 25mg N NH 50mg

S1706 Lamivudine Synonyms: 3TC, Zeffix, Heptovir, Epivir, Epivir-HBV Size Price

O S OH Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor with an IC50 of 2.7 mM. The 25mg pH-driven uptake of TEA by BBMV (pHin = 6.0, pHout = 7.5) was inhibited by lamivudine. The IC50 value for O NN the concentration-dependent effect of lamivudine on TEA uptake by BBMV after 30 s was 2668 μM whereas 50mg IC50 values for cimetidine and trimethoprim were < 2.5 μM and < 25 μM, respectively. H2N 100mg

 Solutions to Signal Transduction Research 8K\KXYK:XGTYIXOVZGYK>GTZNOTKU^OJGYK9KXUZUTOTXK[VZGQK Others

S1719 Zalcitabine Synonyms: Hivid, Dideoxycytidine, NSC 606170 Size Price

O Zalcitabine is a NARTI. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl 100mg HO NH2 N group in position 3’ with hydrogen. This active metabolite works as a substrate for HIV reverse transcriptase, N and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing 200mg hydroxyl group. O 500mg Xanthine oxidase

S1631 Allopurinol Sodium Synonyms: Lopurin, Zyloprim, Aloprim Size Price H N O Allopurinol Sodium (Aloprim) is a xanthine oxidase inhibitor with an IC50 of 7.82±0.12 μM. It is a structural 10mg Na+ isomer of hypoxanthine. It inhibits conversion of xanthine to uric acid and increases reutilization of N hypoxanthine and xanthine for nucleic acid synthesis, thereby decreasing uric acid levels in both serum and 50mg urine. HN N 200mg S1630 Allopurinol Synonyms: Aloprim, Lopurin, Zyloprim Size Price O Allopurinol (Zyloprim) is a xanthine oxidase inhibitor with an IC50 of 7.82±0.12 μM. The inhibition of XO activity 10mg N by 6-aminopurine (IC50=10.89±0.13 μM) and its analogues was compared with that by allopurinol NH (IC50=7.82±0.12 μM). Among these analogues, 2-chloro-6(methylamino) purine (IC50=10.19±0.10 μM) and 50mg N N 4-aminopyrazolo[3,4-d] pyrimidine (IC50=30.26±0.23 μM) were found to be potent inhibitors of XO. H 200mg S1547 Febuxostat Synonyms: TMX-67, Adenuric, Uloric Size Price

N OH Febuxostat is a non-purine selective XAO inhibitor with IC50 of 114 -210 nM. It works by non-competitively 10mg N blocking the channel leading to the active site on xanthine oxidase. Xanthine oxidase is needed to S O successively oxidize both hypoxanthine and xanthine to uric acid. Hence, febuxostat inhibits xanthine oxidase, 25mg O therefore reducing production of uric acid. 50mg

Serotonin reuptake

S1372 Citalopram HBr Synonyms: Celexa, Cipramil Size Price F

O Citalopram (Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) 25mg class. Most often used to treat major depression, it is also used on occasion in the treatment of body N dysmorphic disorder, anxiety, and panic disorder. 50mg

HBr N 200mg

S1869 Dapoxetine HCl Synonyms: Priligy, LY-210448 hydrochloride Size Price

HCl O Dapoxetine hydrochloride is a short-acting novel selective serotonin reuptake inhibitor marketed for the 25mg

O treatment of premature ejaculation in men. The treatment of PE consists of primarily off-label use of oral O N selective serotonin reuptake inhibitors (SSRIs) via either on-demand or daily delivery. 50mg

100mg S1333 Fluoxetine HCl Synonyms: Prozac, Sarafem Size Price

F Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. Fluoxetine is used to the 25mg F HCl treatment of major depression (including pediatric depression), obsessive-compulsive disorder, bulimia F 50mg nervosa, panic disorder and premenstrual dysphoric disorder. O N H 100mg S1336 Fluvoxamine maleate Synonyms: Luvox Size Price

NH O 2 Fluvoxamine is a potent and selective serotonin reuptake inhibitor with approximately 100-fold affinity for the N O 100mg CO2H serotonin transporter over the norepinephrine transporter. It has negligible affinity for the dopamine transporter

F CO2H Z–*$ 200mg F F 1g S1436 Tianeptine sodium Synonyms: Stablon, Coaxil, Tatinol Size Price O N O S Tianeptine is a selective serotonin reuptake enhancer drug used for treating major depressive episodes. 10mg Cl Unlike conventional tricyclic antidepressants, tianeptine enhances the reuptake of serotonin instead of NH inhibiting it, opposite to the action of SSRIs. Moreover, it enhances the extracellular concentration of dopamine 50mg in the nucleus accumbens and modulates the D2 and D3 dopamine receptors. There is also action on the NaO NMDA and AMPA receptors. 100mg O Toll Free:(877)796-6397 www.selleckchem.com [email protected] ---USA and Canada only---  +1-832-582-8158 Others 6NUYVNUJOKYZKXGYK

Phosphodiesterase

S1895 Dipyridamole Synonyms: Permole, Persantine, Dipyridan Size Price

OH Dipyridamole, a phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes 10mg N N N and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. N OH 25mg HO N Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of N N N cAMP, an inhibitor of platelet function. 50mg OH

S1673 Aminophylline Synonyms: Somopphyllin, Aminocadol, Phyllocontin, Truphylline Size Price

O O H H N Aminophylline is a competitive nonselective phosphodiesterase inhibitor with an IC50 of 0.12 mM and also a 10mg N N N nonselective adenosine receptor antagonist. It is a bronchodilator. It is a compound of the bronchodilator O N N O N N theophylline with ethylenediamine in 2:1 ratio. 25mg

NH2 50mg H2N

S1455 Cilomilast Synonyms: Ariflo, SB-207499 Size Price

NC ~***„ <|C""'ƒ$~[„ < 10mg O Œ„ <¶€|C""'ƒ$^"<__¶€ 50mg COOH LPDE4, but Cilomilast is 100-fold less potent against HPDE4. This profile suggests that Cilomilast(SB-207499) O H retain the anti-inflammatory activity of rolipram yet have a decreased tendency to produce side effects. 200mg S2312 Icariin Size Price

O OH } * „ ] }~]" * $"Z "$]Z $ )' * „ ];Z ;Z ;?Z 10mg O O O respectively. It enhances the production of bioactive nitric oxide, as well as mimicking the effects of HO OH O testosterone. It also shows antioxidant, antidepressant and nootropic effects. 25mg OH OH O OH O

OH 100mg OH S2320 Luteolin Synonyms: 3',4',5,7-Tetrahydroxyflavone, Luteoline, Luteolol Size Price

OH

OH Luteolin is a PDE4 inhibitor and a general phosphodiesterase inhibitor, and an Interleukin 6 inhibitor. It 25mg significantly reversed the xylazine/ketamine-induced anesthesia in mice. Luteolin is thought to play an HO O important role in the human body as an antioxidant, a free radical scavenger, an agent in the prevention of 50mg inflammation, a promoter of carbohydrate metabolism, and an immune system modulator. 100mg OH O S2484 Milrinone Synonyms: Primacor Size Price

N N Milrinone is a potent and selective phosphodiesterase 3 inhibitor with an IC50 of 0.42 μM for the inhibition of 10mg FIII PDE. It potentiates the effect of cAMP. It also enhances relaxation of the left ventricle by increasing Ca2+-ATPase activity on the cardiac sarcoplasmic reticulum. It is used in the management of heart failure only 25mg N O when conventional treatment with vasodilators and diuretics has proven insufficient. H 50mg S2131 Roflumilast Synonyms: Daxas Size Price

Cl Roflumilast is a selective, long-acting the enzyme PDE-4 inhibitor with an IC50 of 0.8 nM. It has 5mg N O antiinflammatory effects. Roflumilast produced several dose-limiting side effects including nausea, diarrhoea O N F and headache, and development is continuing in an attempt to minimise the incidence of side effects while 10mg H Cl retaining clinical efficacy. O F 25mg

S1430 Rolipram Synonyms: ZK 62711, SB 95952, ME-3167, Adeo Size Price

O Rolipram is a PDE4-inhibitor. Like most PDE4-inhibitors, it is an anti-inflammatory drug. Rolipram is being 25mg NH studied as a possible alternative to current antidepressants. Recent studies show that rolipram may have antipsychotic effects. 50mg O 100mg O S2127 S-(+)-Rolipram Size Price O S-(+)-Rolipram is a less active enantiomer of the PDE4 inhibitor with an EC50 of 1.0 μM. It is an 5mg anti-inflammatory drug. Rolipram is being studied as a possible alternative to current antidepressants. Recent O O studies show that rolipram may have antipsychotic effects. It displays activity 10-fold less than R-rolipram at 10mg inhibition of PDE IV. NH 25mg

 Solutions to Signal Transduction Research 6NUYVNUJOKYZKXGYK'IKZ_RINUROTKYZKXGYK Others

S1512 Tadalafil Synonyms: Cialis, GF 196960, IC 351, ICOS 351 Size Price

O H 50mg N Tadalafil is a PDE inhibitor. Tadalafil, which has demonstrated a high level of selectivity for PDE5 over the

N N other phosphodiesterases, has shown efficacy in improving erectile function and sexual satisfaction in phase H 100mg O III trials. PDE11A3, PDE11A2, and PDE11A1, which contain progressively shorter N-termini, were more sensitive than PDE11A4 to inhibition by Tadalafil. 500mg O O S2515 Vardenafil Synonyms: Vivanza Size Price O Vardenafil is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively. Chronic 10mg O O HN N S N vardenafil treatment improves erectile function via structural maintenance of penile corpora cavernosa in rats N N 25mg N with acute arteriogenic erectile dysfunction. O 50mg S1550 Pimobendan Synonyms: Vetmedin, Acardi, pimobendane Size Price

Pimobendan is a Ca2+ sensitizer with an IC50 of 26 μM and a selective phosphodiesterase III inhibitor with an 100mg O NH IC50 of <1 μM. Pimobendan decreased the catecholamine secretion (IC(50)=29.5 μM) elicited by carbachol, HN N 200mg N an agonist at nicotinic acetylcholine receptors, but not that elicited by veratridine, an activator of voltage-dependent Na(+) channels, or by high K+, an activator of voltage-dependent Ca2+ channels. O 500mg

S1504 Dyphylline Synonyms: Neothylline, Lufyllin, diprophylline Size Price

OH

O Dyphylline is a xanthine derivative with bronchodilator and vasodilator effects. It is used in the treatment of 10mg OH N respiratory disorders like asthma, cardiac dyspnea, and bronchitis. It acts as an adenosine receptor antagonist N and phosphodiesterase inhibitor. 50mg O N N

S2340 Papaverine HCl Synonyms: Pavabid, Artegodan, Cepaverin, Optenyl, Pavagrant Size Price

O Papaverine hydrochloride, an alkaloid found in opium but not closely related to the other opium alkaloids in its 10mg O structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of O impotence and as a vasodilator, especially for cerebral vasodilation. It apparently can inhibit 25mg N HCl phosphodiesterases and it may have direct actions on calcium channels. O 50mg S1431 Sildenafil citrate Synonyms: Viagra, Revatio Size Price

O N O HN O N S Sildenafil citrate is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. It acts by 10mg N N O inhibiting cGMP specific phosphodiesterase type 5, an enzyme that regulates blood flow in the penis. Sildenafil N 25mg OH has been the prime treatment for erectile dysfunction. O O OH OH HO 50mg O

Acetylcholinesterase

S2251 (-)-Huperzine A Size Price

|ƒ[€•;;\' ;}~]"*#)'* NH2 1mg NMDA-induced current. The IC50 values of huperzine A were neither altered by changing the concentrations *|"$)'ƒ[|$<#$ƒ–€Z*›Ç|])'ƒ 2.5mg H (5 mM) to the external solution. HN 5mg O

S2462 Donepezil HCl Synonyms: Aricept Size Price

HCl O Donepezil hydrochloride is a centrally acting reversible acetylcholinesterase inhibitor with an IC50 of 12.3 nM. 10mg O Its main therapeutic use is in the treatment of Alzheimer’s disease where it is used to increase levels of cortical O N acetylcholine. It has an oral bioavailability of 100% and easily crosses the blood-brain barrier. 25mg

50mg

S2285 Cryptotanshinone Page 74

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S1608 Pyridostigmine Bromide Synonyms: Mestinon, Regono Size Price

Pyridostigmine Bromide is a parasympathomimetic and a reversible cholinesterase inhibitor. It is a quaternary N O 10mg N+ carbamate inhibitor of cholinesterase that does not cross the blood-brain barrier, and it is taken daily in - Br anticipation of an attack, which carbamylates about 30% of peripheral cholinesterase enzyme. 50mg O 100mg Adrenergic receptor

S2458 Clonidine HCl Synonyms: Catapres,Clonidine Size Price Cl H ~   ]" * "$"/"$" $ } 10mg N N *   $ 25mg HN decreases presynaptic calcium levels, and inhibits the release of norepinephrine. Cl 50mg HCl S1324 Doxazosin mesylate Synonyms: Cardura, Carduran, Cardura XL Size Price

O –•Z¶€•€Z€ 100mg O O O N €$}*

N N membrane of vascular smooth muscle cells. 200mg N O H2N HO O S 1g O S2126 Naftopidil Synonyms: Flivas, KT-611, BM-15275, Avishot Size Price

O \* * $  € ]‘$? ' * *$ ** * 25mg *|”#Z"""”Z]""'ƒ$\*– O N N strips precontracted with norepinephrine concentration-dependently, and it shifts the concentration-response 50mg OH curve of norepinephrine in a parallel manner to the right. 100mg S2495 Oxymetazoline HCl Size Price

š–•$}€ 25mg N a topical decongestant in nasal sprays. The action of oxymetazoline results in vasoconstriction. In addition, 50mg HO N the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic H $ 100mg HCl S2507 Salbutamol sulfate Synonyms: Albuterol, Ventolin, Aerolin, Ventorlin, Asthalin, Asthavent Size Price

OH H €}~]"*‘$_?3'$€€ 100mg N OH €*$€–€€ the S isomer blocks metabolism pathways while the R isomer shows activity. 200mg OH

H2SO4 250mg S2516 Xylazine Synonyms: Rompun Size Price

H °•*$}* 10mg N N central and peripheral nervous systems as an a 2-adrenergic agonist. It is used primarily for sedation, 25mg S anesthesia, analgesia and muscle relaxation. 50mg S1206 Bisoprolol Fumarate Synonyms: Zebeta Page 83

 Solutions to Signal Transduction Research .OYZGSOTKGTZGMUTOYZ Others

Histamine

S1291 Cetirizine di HCl Synonyms: Zyrtec, Reactine Size Price O Cl O N OH Cetirizine, an antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse 200mg N agonist used in the treatment of allergies, hay fever, angioedema, and urticaria. 500mg 2HCl 1g S1816 Chlorpheniramine maleate Synonyms: Chlor-Trimeton, Allergisan, Piriton, Teldrin Size Price Cl Chlorpheniramine maleate，a histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, 100mg

and asthma. It is one of the most widely used of the classical antihistaminics. It blocks the action of C4H4O4 endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by 200mg N N histamine. 500mg S1845 Cimetidine Synonyms: Tagamet, SKF-92334, Tratul, Tametin, Dyspamet, Acinil Size Price

HN N Cimetidine, a histamine congener, it competitively inhibits histamine binding to histamine H2 receptors. It 200mg inhibits gastric acid secretion, as well as pepsin and gastrins output. It also blocks the activity of cytochrome N CN 500mg S HN P-450 which might explain proposals for use in neoadjuvant therapy. HN 1g S1847 Clemastine Fumarate Synonyms: Tavist, Xolamin, Agasten, Aloginan Size Price O OH Clemastine is a selective histamine H1 antagonist and binds to the histamine H1 receptor. It blocks the action HO 25mg Cl of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on O N O by histamine. 50mg

100mg

S1245 Dimebon Synonyms: Latrepirdine, Dimebolin Size Price

N Latrepirdine is an antihistamine drug. Latrepirdine operates through multiple mechanisms of action, blocking 5mg N the action of neurotoxic beta-amyloid proteins, inhibiting L-type calcium channels, modulating the action of 2HCl AMPA and NMDA glutamate receptors, exerting a neuroprotective effect by blocking a novel target that 25mg Z€*€Z][~Z][];Z 100mg N and 5-HT6.

S1866 Diphenhydramine HCl Synonyms: Benadryl, Dimedrol, Daedalon Size Price

Diphenhydramine hydrochloride, a histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses 10mg HCl and pruritus. Diphenhydramine competes with free histamine for binding at HA-receptor sites. This 25mg N antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms O brought on by histamine HA-receptor binding. 50mg

S1358 Loratadine Synonyms: Alavert, Claritin Size Price

Cl Loratadine is an antihistamine drug used to treat allergies, and marketed for its non-sedating properties. 100mg N Loratadine is a tricyclic antihistamine, which selectively antagonizes peripheral histamine H1-receptors. Loratadine has a long-lasting effect. 1g N OO 5g

S1890 Nizatidine Synonyms: Tazac, Axid, Axid AR Size Price

CHNO2 10mg HN Nizatidine is a histamine H2-receptor antagonist with and IC50 of 6.7 nM for AChE. The relative anti-AChE HN *Š”•”””*$*;~ 50mg S by nizatidine was noncompetitive, with a Ki value of 7.4 x 10 nM.

S N 200mg

N

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S2494 Olopatadine HCl Synonyms: Opatanol, Pataday, Patanase, Allelock Size Price

O Olopatadine hydrochloride is a histamine blocker and mast cell stabilizer with an IC50 of 559 μM for the 25mg O release of histamine. Evaluation of the interaction of olopatadine with histamine receptors revealed a relatively 50mg OH high affinity for the H1 receptor (Ki = 31.6 nM, pKi = 7.5 ± 0.1) but lower affinities for H2 receptors (Ki = 100 μM, pKi = 4.0 ± 0.19) and H3 receptors (Ki = 79.4 μM, pKi = 4.1 ± 0.16,). N 100mg HCl S1801 Ranitidine HCl Synonyms: Zantac, AH 19065, Azantac Size Price

H H Ranitidine hydrochloride(Zantac) is a histamine H2-receptor antagonist with IC50 of 3.3 ± 1.4 μM. It inhibits O N N 10mg N S stomach acid production. It is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions such as hives. It has 10% the affinity that cimetidine has to CYP450 so it causes fewer side NO2 25mg HCl effects, but other H2 blockers famotidine and nizatidine have no CYP450 significant interactions. 50mg GABA

S2269 Baicalin Size Price

O OH OH O Baicalin is a known prolyl endopeptidase inhibitor and affects the GABA receptors. It is a flavone, a type of 10mg HO HO O flavonoid. It is found in several species in the genus Scutellaria, including Scutellaria lateriflora. There are 10 mg/g baicalin in Scutellaria galericulata leaves. It is a component of Chinese medicinal herb Huang-chin. 25mg HO O O OH 50mg

S1329 Etomidate Synonyms: Amidate Size Price

O Etomidate is a GABAA receptors agonist at GABAA receptors. Etomidate is a short acting intravenous 10mg

O N anaesthetic agent used for the induction of general anaesthesia and for sedation for short procedures such as reduction of dislocated joints and cardioversion. 50mg N 500mg S1338 Gabapentin HCl Synonyms: Gabarone, Neurontin Size Price O OH .HCl Gabapentin Hydrochloride is a GABA analogue. It was used for the treatment of epilepsy, and currently, 1g

gabapentin is widely used to relieve pain, especially neuropathic pain. 10g

NH2

S2133 Gabapentin Synonyms: Fanatrex, Gabarone, Neurontin Size Price

O OH Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the 25mg treatment of epilepsy, and currently, gabapentin is widely used to relieve pain, especially neuropathic pain. 50mg NH 2 100mg S1589 SKF 89976A HCl Size Price

HCl ‘__#;;^;}~]"*"$?Z]]"Z_<<")'*;Z 10mg N OH rGAT-2, hGAT-3 and hBGT-1 respectively. It is selective for GAT-1. It inhibits transport current competitively O | )'ƒ €  | "$"? 'ƒ$ ; ^^^ * 50mg systemic administration and is active in vivo. 100mg

 Solutions to Signal Transduction Research Peptide inhibitors

CDK ...... 100 Bcl-2 ...... 100 p38 MAPK ...... 100 JNK ...... 100 Oxytocin receptor ...... 100 Glycoprotein receptor ...... 101 vasopressin receptor ...... 101 LHRHR/GnRHR ...... 101 PTHR ...... 102 Melanocortin-1 receptor ...... 103 PKC ...... 103 SNAPR...... 103 NKR...... 103 BDKR/KOR...... 103 TRH receptor...... 104 CRF receptor...... 104 GRF-R...... 104 Ghrelin receptor...... 104 tachykinin NK1 receptor...... 105 Angiotensin receptor...... 105 Secretin receptor...... 105 SSTR...... 105 GCGR...... 105 GHSR...... 106

Peptides )*1(IRV3'610415^_ZUIOTXKIKVZUX

CDK

P1077 [Ala92]-p16 (84-103) Size Price

Asp-Ala-Ala-Arg-Glu-Gly-Phe- [Ala92]-p16 (84-103) is a peptide derived from the tumor suppressor protein p16. [Ala92]-p16 (84-103) can 1mg Leu-Ala-Thr-Leu-Val-Val-Leu- bind to cdk6. The aberrant p16 RNA transcripts encoded key peptides (amino acids 84-103) involved in His-Arg-Gly-Arg·AcOH binding with CDK4. Over-expression of these aberrant p16 RNA transcripts resulted in decreased cell proliferation rate, enlargement of cell shape and reduced level of hyperphosphorylated forms of pRb. Bcl-2

P1078 Bax inhibitor peptide P5 Size Price

Pro-Met-Leu-Lys-Glu·AcOH Bax inhibitor peptide P5 is a cell-permeable synthetic Bax peptide inhibitor. Bax inhibitor peptide P5 is 1mg designed from Ku70 that is suggested to suppress the mitochondrial translocation of Bax. Bax inhibitor peptide P5 inhibits Bax-mediated apoptosis in vitro. P1079 Bax inhibitor peptide V5 Size Price

Val-Pro-Met-Leu-Lys·AcOH Bax inhibitor peptide V5 is a cell-permeable synthetic Bax peptide inhibitor. Bax inhibitor peptide V5 is 1mg designed from Ku70 that is suggested to suppress the mitochondrial translocation of Bax. Bax inhibitor peptide V5 inhibits Bax-mediated apoptosis in vitro. P1080 Bax inhibitor peptide Size Price

Ile-Pro-Met-Ile-Lys·AcOH Bax inhibitor peptide,negative control is a negative control peptide for the Bax inhibitor peptides V5 and P5, 1mg which inhibit Bax translocation to mitochondria and Bax-mediated apoptosis in vitro.

p38 MAPK

P1081 JIP-1(153-163) Size Price

Arg-Pro-Lys-Arg-Pro-Thr-Thr- Peptide inhibitor of c-Jun N-terminal kinase (JNK), based on residues 153-163 of JNK-interacting protein-1 1mg (JIP-1). Binds to JNK with affinity in the micromolar range and minimally inhibits p38 and ERK. Leu-Asn-Leu-Phe-NH2·AcOH JNK

P1081 JIP-1(153-163) Page 100

Oxytocin receptor

P1025 Atosiban Synonyms: Tractocile, Antocin Size Price

c[Mpa-D-Tyr(Et)-Ile-Thr-Asn- Atosiban is an inhibitor of the hormones oxytocin (IC50=59 nM) and vasopressin. Atosiban had nanomolar 100mg affinity for rat and human oxytocin receptors but was much less selective vs. vasopressin receptors. Atosiban Cys]-Pro-Orn-Gly-NH2·AcOH was found to be 70-fold more potent at human recombinant V1a receptors than at human OT receptors and 500mg was only 10-fold and 30-fold selective for human OT vs. human V1b and V2 receptors. 1g

P1029 Oxytocin Synonyms: Pitocin, Syntocinon Size Price

Cys-Tyr-Ile-Gln-Asn-Cys- Oxytocin is a nine amino acid peptide that is synthesized in hypothalamic neurons and transported down 100mg axons of the posterior pituitary for secretion into blood. It is released in large amounts after distension of the Pro-Leu-Gly-NH2·AcOH (Disulfide bridge: Cys1-Cys6) cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and breastfeeding. 500mg 1g

 Solutions to Signal Transduction Research -R_IUVXUZKOTXKIKVZUX'XMOTOTK\GYUVXKYYOTXKIKVZUX -UTGJUZXUVOTXKRKGYOTMNUXSUTKXKIKVZUX Peptides

Glycoprotein receptor

P1011 Eptifibatide Synonyms: Integrilin Size Price

c(Map-Har-Gly-Asp-Trp- Eptifibatide is a 6 amino acid peptide. It binds to the platelet receptor glycoprotein IIb/IIIa of human platelets 100mg and inhibits platelet aggregation. One study shows the inhibition of platelet glycoprotein IIb/IIIa in acute Pro-Cys)-NH2·AcOH coronary syndromes. 500mg

1g Arginine vasopressin receptor

P1025 Atosiban Synonyms: Tractocile, Antocin Page 100

P1047 Felypressin Synonyms: felypressin, Octapressin Size Price

H-[Cys-Phe-Phe-Gln-Asn- Felypressin is a Vasopressin 1 agonist and a peptide containing eight amino acids including cystine. It will thus 10mg have affects at all Arginine vasopressin receptor 1As. It will, however, have its main physiological effects on Cys]-Pro-Lys-Gly-NH2·AcOH vascular SMC’s due to the form in which it is administered. 25mg

50mg

P1015 Lypressin Synonyms: ZM Lysine 252868, Vasopressin AG 1517, Tyrphostin AG 1517 Size Price

Cys-Tyr-Phe-Gln-Asn-Cys- Lypressin is a synthetic analog of the pituitary hormone, argipressin. Its action is mediated by the vasopressin 100mg receptor V2. It modulates levels of circulating Factor VIII and Von Willebrand factor. Lypressin is a hormone Pro-Lys-Gly-NH2·AcOH (Disulfide bridge: Cys1-Cys6) used to prevent or control the frequent urination, increased thirst, and loss of water associated with diabetes 500mg insipidus. 1g P1028 Ornipressin Size Price

c[Cys-Tyr-Phe-Gln-Asn-Cys]- Ornipressin is a vasopressin agonist specific for the V1 receptor. It is a synthetic analog of vasopressin with 25mg Orn-Gly-NH ·AcOH ornithine in position 8 of the cyclic nonapeptide. 2 100mg

500mg

P1034 Terlipressin Synonyms: Glypressin, Haemopressin, Variquel Size Price

Cly-Cly-Gly-Cys-Tyr-Phe- Terlipressin is similar to a naturally occurring hormone present in the body, known as ADH or vasopressin and 100mg Gln-Asn-Cys-Pro-Lys-Gly- contains 12 amino acids. Terlipressin is an analogue of vasopressin used as a vasoactive drug in the management of hypotension. Terlipressin is also a nonselective agonist of V1 vasopressin receptors, but it has 500mg NH2·AcOH a longer half-life and a lower incidence of ischaemic complications. 1g P1020 Vasopressin Synonyms: Arginine vasopressin, argipressin, antidiuretic hormone Size Price

Cys-Tyr-Phe-Gln-Asn-Cys- Vasopressin is a synthetic analog of the pituitary hormone. Its action is mediated by the vasopressin receptor 100mg Pro-Arg-Gly-NH ·AcOH V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor 2 500mg (Disulfide bridge: Cys1-Cys5) VIII and von willebrand factor. 1g Gonadotropin-releasing hormone receptor

P1023 Alarelin Synonyms: BMS-582664 Size Price

Glp-His-Trp-Ser-Tyr-D-Ala- Alarelin is a synthetical nonapeptide similarity of LHRH. It is used to treat endmometriosis. The inhibitory effect 25mg Leu-Pro-NHEt·AcOH *Œ[‚[;¶€**"")$–€** cell proliferation was achieved a concentration of 10 mM and it acted in a dose-dependent manner. 500mg

1g

P1019 Cetrorelix Acetate Synonyms: Cetrotide Size Price

Cetrorelix Acetate is a potent GnRH receptor antagonist (KD = 0.2 nM, IC50 = 1.2 nM). It suppresses Ac-3-(2-naphthyl)-D-Ala-4- 1mg Chloro-D-Phe-3(3-pyridyl)- production of luteinizing hormone and follicle-stimulating hormone from the pituitary gland, which inhibits D-Ala-Ser-Tyr-D-Cit-Leu- ovulation and exhibits antiproliferative effects and displays efficacy against hormone-sensitive cancers in vivo. 5mg

Arg-Pro-D-Ala-NH2 500mg

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P1021 Deslorelin Synonyms: Ovuplant Size Price

Pyr-His-Trp-Ser-Tyr-D- Deslorelin is a potent LHRH and GnRH agonist, and induces ovulatin in mares. It is commonly used to induce 100mg Trp-Leu-Arg-Pro-NHEt ovulation in cycling mare. Deslorelin acetate was more effective in inducing ovulation in the July and August ·AcOH (95.4%) and September and October (95.7%) than in the March and April (81.1%). Mares treated in May 500mg through October also experienced shorter intervals to ovulation than mares treated in March and April. 1g

P1048 Fertirelin Size Price

Pyr-His-Trp-Ser-Tyr-Gly- Fertirelin is a synthetic LHRH analogue, and it is a potent LHRH agonist. After a transient increase, continuous 10mg Leu-Arg-Pro-NHEt·AcOH administration results in downregulation of LH and FSH levels followed by a suppression of ovarian and testicular steroid biosynthesis. 25mg

50mg

P1026 Gonadorelin Synonyms: Factrel Size Price

Glp-His-Trp-Ser-Tyr-Gly-Leu- Gonadorelin is a tropic peptide hormone responsible for the release of FSH and LH from the anterior pituitary. 100mg It is synthesized and released from neurons within the hypothalamus. After a transient increase, continuous Arg-Pro-Gly-NH2·AcOH administration results in downregulation of LH and FSH levels followed by a suppression of ovarian and 500mg testicular steroid biosynthesis. 1g

P1060 Lecirelin Size Price

Pyr-His-Trp-Ser-Tyr-D- Lecirelin is a synthetic GnRH analogue. Lecirelin is a nonapeptide, while the natural compound is a 1mg Tle-Leu-Arg-Pro-NHEt decapeptide; moreover the glycine aminoacid in the 6th position has been substituted by leucine. ·AcOH 10mg

25mg P1013 Leuprorelin Synonyms: Lucrin,Lupron,Prostap Size Price

Pyr-His-Trp-Ser-Tyr-D- Leuprorelin is a gonadotropin-releasing hormone agonist. It acts at pituitary GnRH receptors. It down regulates 100mg Leu-Leu-Arg-Pro-NHEt the secretion of gonadotropins LH and FSH leading to a dramatic reduction in estradiol levels. It is a drug that ·AcOH mimics the action of a hormone called gonadotrophin releasing hormone. 500mg

1g P1061 Nafarelin Size Price

Pyr-His-Trp-Ser-Tyr-D-2- Nafarelin is a GnRH agonist which acts as an analog of GnRH and is a synthetic decapeptide. Nafarelin 100mg increases the release of FSH and LH by the anterior pituitary, which in turn leads to an increase of Nal-Leu-Arg-Pro-Gly-NH2 ·AcOH estrogen/progesterone. When administered, Nafarelin has the purpose of causing increase estrogen that will 500mg negatively feed back upon hypothalamus to decrease GnRH. 1g P1037 Triptorelin Synonyms:Synonyms: Decapeptyl,ZM 252868, Dekapeptil, AG 1517, Diferelin, Tyrphostin Diphereline AG 1517 Size Price

Triptorelin is a synthetic analogue of gonadorelin with amino acid (D-tryptophan) substitution in position 6 to Pry-His-Trp-Ser-Tyr-D- 100mg inhibit rapid degradation for long activity. Triptorelin is a GnRH agonist. By causing constant stimulation of the Trp-Leu-Arg-Pro-Gly-NH2 pituitary, it decreases pituitary secretion of gonadotropins LH and FSH. 500mg

1g Parathyroid hormone receptor

P1033 Teriparatide Synonyms: hPTH 1-34, Parathar Size Price

Teriparatide is recombinant parathyroid hormone, identical to the 34 N-terminal amino acids of human Ser-Val-Ser-Glu-Ile-Gln-Leu-Met- 25mg His-Asn-Leu-Gly-Lys-His-Leu-Asn- parathyroid hormone. It reduces bone turnover, stimulates the formation of new bone, and increases bone mass. It binds to the same receptors as PTH and is known to exert effects identical to that of PTH on the bone Ser-Met-Glu-Arg-Val-Glu-Trp-Leu- 100mg Arg-Lys-Lys-Leu-Gln-Asp-Val-His- and the kidney. Asn-Phe·AcOH 500mg

 Solutions to Signal Transduction Research 3KRGTUIUXZOT6XUZKOTQOTGYK)9UR[HRKTYLGZZGINSKTZVXUZKOTXKIKVZUX 4K[XUQOTOTXKIKVZUX(XGJ_QOTOTXKIKVZUX1GVVGUVOUOJXKIKVZUX Peptides

Melanocortin-1 receptor

P1073 Melanotan I Synonyms: afamelanotide Size Price

Ac-Ser-Tyr-Ser-Nle-Glu- Melanotan I is a synthetic analog of the naturally occurring melanocortin peptide hormone alpha-melanocyte 5mg His-D-Phe-Arg-Trp-Gly-Lys- €|'[ƒ€€ thereby subsequently reduce UV damage to UV exposed skin in preliminary studies. 10mg Pro-Val-NH2·AcOH

25mg

P1064 PT-141 Synonyms: Bremelanotide,PT141 Size Price

Ac-Nle-Asp-His-D-Phe-Arg- PT-141 is an agonist of the melanocortin-1 receptor which is located on melanocyte cells but it does not bind 10mg Trp-Lys-OH·AcOH well to any other receptors. It is a cyclic hepta-peptide lactam analog of alpha-melanocyte-stimulating Asp-Lys hormone. 50mg

500mg Protein kinase C

P1083 ZIP Size Price

Myr-Ser-Ile-Tyr-Arg-Arg- ›}„Z*'#Z€Z„~• 1mg Gly-Ala-Arg-Arg-Trp-Arg- Œ„$„'#€ Leu·AcOH $‚Œ„|}~]" $])'ƒ€* following central administration in vivo. Soluble nsf attachment protein receptor

P1001 Argireline Synonyms: Acetyl hexapeptide-3 Size Price

Ac-Glu-Glu-Met-Gln-Arg- Argireline Acetate is a synthetic anti-aging cosmetic derived from natural proteins. NAP receptor complex s 500mg necessary for the contraction of muscles. It also slows or even stops the excessive release of catecholamine, Arg-NH2 which is known to help in wrinkle formation. 1g

10mg Neurokinin receptor

P1044 Eledoisin Size Price

pGlu-Pro-Ser-Lys-Asp-Ala- Eledoisin Acetate is an acetate salt form of Eledoisin which is a decapeptide from the posterior salivary gland 5mg of a species of snail and a nonselective neurokinin receptor agonist. It has vasodilator, hypotensive and Phe-Ile-Gly-Leu-Met-NH2 ·AcOH extravascular smooth muscle stimulant properties. 10mg

25mg Bradykinin receptor/Kappa opioid receptor

P1043 Dynorphin A(1-13) Size Price

Tyr-Gly-Gly-Phe-Leu-Arg- Dynorphin A (1-13) Acetate is an acetate salt form of Dynorphin A (1–13) which is an extraordinarily potent 5mg Arg-Ile-Arg-Pro-Lys-Leu- opioid peptide and acts on the bradykinin receptor and a major metabolite of Dynorphin A. The N-terminal ·AcOH tyrosine of dynorphin A is necessary to activate opioid receptors such as KOR, but is unnecessary in binding 25mg to bradykinin receptors. 100mg

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Thyrotropin-releasing hormone receptor Ghrelin receptor

P1066 Taltirelin Synonyms: L-Prolinamide, Taltirelin hydrate, TA-0910 Size Price

1-methyl-4,5-dihydroorotyl- Taltirelin is a TRH analog, which mimics the physiological actions of TRH, but with a much longer half-life and 100mg duration of effects, and little development of tolerance following prolonged dosing. It displays 30 - 100-fold His-Pro-NH2·AcOH more potent CNS activity and 50-fold weaker endocrine activity than TRH. 500mg

1g Corticotropin releasing factor receptor

P1041 CRF(human, rat) Size Price

CRF is a 41-peptide amide which stimulates the release of ACTH. It inhibits food intake in mammals. CRF H-Ser-Glu-Glu-Pro-Pro-Ile-Ser- 10mg Leu-Asp-Leu-Thr-Phe-His-Leu- plays a potent role in decreasing food intake in avian species. The suppressive effect on food intake was strongest for CRF followed by urotensin I, then urocortin. Leu-Arg-Glu-Val-Leu-Glu-Met- 50mg Ala-Arg-Ala-Glu-Gln-Leu-Ala- Gln-Gln-Ala-His-Ser-Asn-Arg- 200mg

Lys-Leu-Met-Glu-Ile-Ile-NH2 ·AcOH

P1042 CRF(ovine) AcF3 Size Price

H-Ser-Gln-Glu-Pro-Pro-Ile-Ser- CRF is a hypothalamic peptide which stimulates ACTH release from the anterior lobe of the pituitary gland. It 10mg Leu-Asp-Leu-Thr-Phe-His-Leu- is a preferential CRF1 receptor agonist. In the placenta, CRH is a marker that determines the length of Leu-Arg-Glu-Val-Leu-Glu-Met- gestation and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the 50mg Thr-Lys-Ala-Asp-Gln-Leu-Ala- onset of parturition. Gln-Gln-Ala-His-Ser-Asn-Arg- 200mg

Lys-Leu-Leu-Asp-Ile-Ala-NH2·AcF3 Growth-hormone-releasing factor receptor

P1072 CJC-1295 Size Price

Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr- CJC-1295 is a long-acting GHRH analog and stimulates GH and IGF-1 secretion. It will keep a steady increase 25mg Gln-Ser-Tyr-Arg-Lys-Val-Leu- of HGH and IGF-1 with no increase in prolactin. CJC-1295 represents a very exciting new compound that has Ala-Gln-Leu-Ser-Ala-Arg-Lys- the potential to increase growth hormone and IGF-I secretion and effects, with a built-in safeguard to limit 50mg Leu-Leu-Gln-Asp-Ile-Leu-Ser- excessive elevations of GH and IGF-1 levels. 100mg Arg-NH2 P1058 GRF (human) Size Price

H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr- GRF is a hypothalamic hormone which regulates the synthesis and secretion of growth hormone from the 100mg Asn-Ser-Tyr-Arg-Lys-Val-Leu- anterior pituitary. It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus. Gly-Gln-Leu-Ser-Ala-Arg-Lys- Anterior pituitaries from the dwarf mouse strain "little" did not release growth hormone or accumulate 500mg Leu-Leu-Gln-Asp-Ile-Met-Ser- adenosine 3’,5’-monophosphate (cyclic AMP) in response to human and rat growth hormone-releasing factor. Arg-Gln-Gln-Gly-Glu-Ser-Asn- 1g Gln-Glu-Arg-Gly-Ala-Arg-Ala-

Arg-Leu-NH2·AcOH Ghrelin receptor

P1059 Hexarelin Size Price

His-D-2-Me-Trp-Ala-Trp- Hexarelin is a powerful GH-releasing peptide and capable of causing profound GH release. (ED50 = 0.48 ± 5mg 0.02 μg/kg) Hexarelin is a six-amino acid peptide. It activates G-protein-coupled receptors (GPCRs) and D-Phe-Lys-NH2·AcOH stimulates growth hormone (GH) secretion from pituitary somatotropes. 10mg

25mg

 Solutions to Signal Transduction Research -NXKROT:GIN_QOTOT41XKIKVZUX'TMOUZKTYOTXKIKVZUX9KIXKZOTXKIKVZUX 9USGZUYZGZOTXKIKVZUX-R[IGMUTXKIKVZUX Peptides

P1075 Ipamorelin Synonyms: NNC-26-0161 Size Price

Aib-His-D-2-Nal-D-Phe- Ipamorelin is a selective growth hormone secretagogue and agonist of the ghrelin receptor. In pentobarbital 25mg anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = Lys-NH2·AcOH 80±42 nmol/kg and Emax = 1545±250 ng GH/ml vs 115±36nmol/kg and 1167±120ng GH/ml). 100mg

200mg

Tachykinin NK1 receptor

P1068 Vapreotide Synonyms: RC-160, Octastatin Size Price

H-D-Phe-Cys-Tyr-D-Trp- Vapreotide is a long-acting somatostatin analog, possesses an analgesic effect. It reduces splanchnic blood 50mg flow and inhibits growth hormone release, and inhibits the release of peptides and vasoactive compounds Lys-Val-Cys-Trp-NH2·AcOH from neuroendocrine tumors. 100mg

500mg

Angiotensin receptor

P1024 Angiotensin Synonyms: Gabarone, Neurontin Size Price

Asp-Arg-Val-Tyr-His-Pro- Angiotensin is an oligopeptide and causes blood vessels to constrict, and drives blood pressure up. It is part 100mg Phe·AcOH of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. It also stimulates the release of aldosterone from the adrenal cortex. 500mg

1g

Secretin receptor

P1038 Secretin Size Price

His-Ser-Asp-Gly-Thr-Phe- Secretin is a hormone that controls the secretions into the duodenum, and an orexin-A binding to 25mg Thr-Ser-Glu-Leu-Ser-Arg- phospholipase C inhibitor (with IC50 in the range from 30 to 100 nM). Its effect is to regulate the pH of the Leu-Arg-Asp-Ser-Ala-Arg- duodenal contents via the control of gastric acid secretion and buffering with bicarbonate. 100mg Leu-Gln-Arg-Leu-Leu-Gln- 500mg Gly-Leu-Val-NH2·AcOH

Somatostatin receptor

P1039 Somatostatin Size Price

Ala-Gly-c[Cys-Lys-Asn-Phe- Somatostatin acetate is an inhibitor of growth and suppresses the release of a variety of other hormones 100mg Phe-Trp-Lys-Thr-Phe-Thr- involved in the regulation of important physiological functions of the gastrointestinal tract. It is a peptide Ser-Cys]·AcOH hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via 500mg interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. 1g

Glucagon receptor

P1056 Glucagon HCl Synonyms: Glukagon novo Size Price

H-His-Ser-Gln-Gly-Thr-Phe- €  * 1mg Thr-Ser-Asp-Tyr-Ser-Lys-Tyr- metabolism. Glucagon has often been called the hyperglycemic-glycogenolytic factor because it causes the Leu-Asp-Ser-Arg-Arg-Ala-Gln- breakdown of liver glycogen to sugar and thereby increases the concentration of sugar in the bloodstream. 5mg Asp-Phe-Val-Gln-Trp-Leu-Met- Asn-Thr-OH·AcOH 25mg

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Growth hormone secretagogue receptor

P1049 GHRP-2 Synonyms: GH Releasing Peptide-2 Size Price

H-D-Ala-D-2-Nal-Ala-Trp- GHRP-2 is a true hGH secretagogue. It is a synthetic agonist of ghrelin, the newly-discovered gut peptide 100mg which binds to the GH secretagogue receptor. Ghrelin has two major effects, stimulating both GH secretion D-Phe-Lys-NH2·AcOH and appetite/meal initiation. GHRP-2 has been extensively studied for its utility as a GHS. 500mg

1g

P1054 GHRP-6 Synonyms: Growth hormone releasing peptide 6 Size Price

H-His-D-Trp-Ala-Trp-D- GHRP-6 is a peptide in the growth factor family. It has strong effect on the release of Growth Hormone. Its 100mg main use is to promote food intake by stimulating hunger and aid in energy metabolism. It has also been Phe-Lys-NH2 discovered that when GHRP-6 and insulin are used simultaneously, GH response to GHRP-6 is increased. 500mg

1g P1075 Ipamorelin Synonyms: NNC-26-0161 Page 105

 Solutions to Signal Transduction Research Alphabetical Product Index



(-)-Huperzine A 95 Anastrozole 61 Bax inhibitor peptide V5 100 [Ala92]-p16 (84-103) 100 Ancobon 25 BAY 73-4506 8,14,50 ?@ 60 Andarine 60 Becenun 25 17-AAG 69 Angiotensin 105 Belinostat 29 17-DMAG 69 AP23573 56 Bestatin 70 2-ME2 16 AP24534 6,11,12,16 BEZ235 54,57 2-Methoxyestradiol 16 Apixaban 91 BI 2536 20 Argireline 103 BIBF1120 10.11 Aromasin 61 BIBR1532 25 ' AS-1404 16 BIBW2992 3,13 AS-605240 53 Bicalutamide 60 A-966492 38 AS703026 47 BIIB021 69 AB1010 6,14 AstraZeneca 61 BIRB 796 48 Abiraterone 88 AT7519 20 Bisoprolol Fumarate 83,96 ABT-263 34 AT7867 58 BIX 02188 47 ABT-378 68 AT9283 11,16,44,74 BIX 02189 47 ABT-737 34 Atazanavir 68 BMS 777607 47 ABT-751 23 Atazanavir sulfate 69 BMS 794833 9 ABT-869 6,16 Atosiban 100 BMS-232632-05 69 ABT-888 38 Aurora A Inhibitor I 42 BMS-354825 12 AC220 15 AV-951 6 BMS-387032 22 AC480 5 Avodart 62 BMS-540215 6 Acetaminophen 78 Axitinib 10,15 BMS-582664 9 Actimid 35 AZ 960 74 BMS-599626 5 Adefovir Dipivoxil 92 AZD0530 11 BMS-707035 65 Adriamycin 22 AZD1152-HQPA 42 BMS-708163 72 AEE788 3,10,13 AZD1480 74 BMS-740808 91 10,15 AG-013736 AZD2171 7 BMS-790052 70 AG-014699 38 AZD2281 38 Bortezomib 68 AG14361 38 AZD6244 47 Bosutinib 12 AG-490 4,74 AZD6482 54 Bredinin 25 Alarelin 101 AZD7762 26 Brivanib 6 Alimta 24 AZD8055 56 Brivanib alaninate 9 Allopurinol 93 AZD8330 47 BS-181 HCl 21 Allopurinol Sodium 93 AZD8931 4 BSI-201 39 Alvespimycin 69 Alvocidib 21 ( ) AM 281 82 Bafetinib 11 Camptosar 22 AMG-208 14 Baicalin 98 Camptothecine 22 AMG-706 8 Barasertib 42 Candesartan 82 Aminophylline 94 Bax inhibitor peptide 100 Canertinib 13 Amlodipine 85 Bax inhibitor peptide P5 100 Capecitabine 24 Amlodipine besylate 85

Capsaicin 82 Cytochrome P450 14a-demethylase inhibitor 1e 88 ENMD-2076 42 Carmustine 25 Cytochrome P450 14a-demethylase inhibitor 1f 88 Entinostat 30 Casodex 60 Cytochrome P450 14a-demethylase inhibitor 1g 88 Enzastaurin 76 CCI-779 56 Cytochrome P450 14a-demethylase inhibitor 1h 89 EPO906 23 CCT129202 42 Cytochrome P450 14a-demethylase inhibitor 1i 89 Epothilone A 23 Cediranib 7 Cytochrome P450 14a-demethylase inhibitor 1j 89 Epothilone B 23 Cetirizine di HCl 97 Cytochrome P450 14a-demethylase inhibitor 1k 89 Eptifibatide 101 Cetrorelix Acetate 101 Cytochrome P450 14a-demethylase inhibitor 1l 89 Erlotinib HCl 4 CGS 20267 61 Cytochrome P450 14a-demethylase inhibitor 1m 89 Esomeprazole magnesium 86 Chelerythrine Chloride 76 Cytochrome P450 14a-demethylase inhibitor 1n 89 Estriol 61 CHIR-258 7,11,14,16 Estybon 20 CHIR-265 8,50 * Etomidate 98 CHIR-99021 57 Etoposide 22 Dacinostat 29 Chlorpheniramine maleat 97 Everolimus 57 Dacogen 24 CHR-2797 70 Evista 61 DAMPA 26 Chrysophanic acid 5,57 Evoltra 24 Danoprevir 70 CI-1033 13 EX 527 31 Danusertib 11,12 CI-1040 47 Exemestane 61 Dapoxetine HCl 93 Cilnidipine 86 Dasatinib 12 Cilomilast 94 Decitabine 24 , Cimetidine 97 Deforolimus 56 Citalopram HBr 93 Fareston 60 Dehydroepiandrosterone 60 CJC-1295 104 Fasudil HCl 20 Deslorelin 102 Cladribine 24 Febuxostat 93 Desmethyl Erlotinib 6 Clemastine Fumarate 97 Felodipine 85 DHEA 60 Clofarabine 24 Felypressin 101 Diclofenac sodium 78 Clolar 24 Fertirelin 102 Didanosine 92 Clonidine 96 Finasteride 62 Dimebon 97 Clonidine HCl 96 Fingolimod 12,91 Diphenhydramine HCl 97 CNF2024 69 Flavopiridol 21 Dipyridamole 94 Colchicine 23 Floxuridine 24 DMXAA(ASA404) 16 CP673451 7 Flucytosine 25 Docetaxel 23 CP-690550 74 Fludara 24 Donepezil HCl 95 CP-724,714 13 Fludarabine 24 Dovitinib 7,11,14,16 CPT 11 22 Fludarabine Phosphate 24 Doxazosin mesylate 96 CRA-02478 30 Fluoxetine HCl 93 Doxorubicin 22 CRF(human, rat) 104 Fluvoxamine maleate 93 Droxinstat 30 CRF(ovine) AcF3 104 Foretinib 9,15 Dutasteride 62 Crizotinib 14 FTY720 12,91 Dynorphin A(1-13) 103 Cryptotanshinone 74,95 Fulvestrant 61 Dyphylline 95 CUDC-101 4,31 CYC116 7,44 - CYC202 21 + Gabapentin 98 Cyclopamine 72 E7080 7 Gabapentin HCl 98 CYT997 23 EKB-569 3 Gantanol 25 Cytarabine 25 Eledoisin 103 GDC-0449 72 Cytochrome P450 14a-demethylase inhibitor 1a 88 Elesclomol 68 GDC-0879 50 Cytochrome P450 14a-demethylase inhibitor 1b 88 Ellence 23 GDC-0941 54 Cytochrome P450 14a-demethylase inhibitor 1c 88 Elvitegravir 65 Gefitinib 3 Cytochrome P450 14a-demethylase inhibitor 1d 88 Emtricitabine 92 Gemcitabine HCl 24 Gemzar 24 0 MDV3100 60 GHRP-2 106 Melanotan I 103 Javlor 23 GHRP-6 106 MG-341 68 JIP-1(153-163) 100 Givinostat 30 MGCD0103 29 JNJ 26854165 35 Gleevec 7,9 MGCD-265 8,15 JNJ-26481585 30 Gliadel 25 Milrinone 94 JNJ-38877605 14 Glucagon HCl 105 Mitoxantrone 22 JNJ-7706621 21,44 Gonadorelin 102 Mitoxantrone 2HCl 25 GRF (human) 104 1 Mizoribine 25 GS-9137 65 MK 3207 HCl 78 Ketoprofen 78 GSK1059615 53,57 MK-0431 69 Ki8751 8,14 GSK1292263 62 MK-0457 44 KRN 633 8 GSK1363089 9 MK-0683 31 KRX-0401 62 GSK1904529A 13 MK-2206 58 KU-0063794 56 GSK429286A 20 MK-2866 60 KU-55933 58 GSK461364 20 MK-5172 70 KU-60019 58 GTx-024 60 MK-0518 65 KW 2449 15,44 GW-572016 3,13 MK-8669 56 GW786034 8 MLN 2238 68 GX15-070 34 2 MLN518 15

Lamivudine 92 MLN8054 43 . Lansoprazole 86 MLN8237 43 Lapatinib Ditosylate 3,13 MLN9708 68 Hesperadin 43 LAQ824 29 Mocetinostat 29 Hexarelin 104 LBH-589 29 Motesanib Diphosphate 8 Hexestrol 61 LDE225 83 MP-470 8,14 HKI-272 4 Lecirelin 102 MS-275 30 HMN-214 20 Lenalidomide 35 Mubritinib 6 HMR-1275 21 Letrozole 61 Hycamtin 22 Leuprorelin 102 4 leurocristine 23 / Nafarelin 102 Leustatin 24 Naftopidil 96 Ibuprofen 78 Linifanib 6,16 Naproxen Sodium 78 IC-87114 53 Lopinavir 68 Navelbine 49 Icariin 94 Loratadine 97 Navitoclax 34 Imatinib 9 Luteolin 94 Nebivolol HCl 83 Imatinib Mesylate 7 LY2228820 49 Neratinib 4 Indirubin 21 LY-231514 24 Nevirapine 92 Iniparib 39 LY2784544 74 Nexavar 9,50 INNO-406 11 LY294002 53 Nilotinib 12 INO-1001 39 LY315920 91 Nimodipine 85 Ipamorelin 105,106 LY317615 76 Nisoldipine 85 Iressa 3 LY335979 91 Nitrendipine 85 Irinotecan 22 LY-450139 72 Nolvadex 60 Irinotecan 22 LY500307 61 Norvir 68 Irinotecan HCl Trihydrate 22 Lypressin 101 NPI-2358 16 Isentress 65 3 NSC 131463 26 Ispinesib 44 NSC 37132 5,57 Maraviroc 65 Isradipine 85 NSC 609699 22 Masitinib 6,14 Istubal 60 NSC 696085 30 ITF2357 30 MC1568 29 NSC-310739 25 PHA-739358 11,12,44 9 NSC-409962 25 PHA-793887 21 NSC-746045 39 Pharmorubicin 23 S-(+)-Rolipram 94 NVP-ADW742 13 PHT-427 57,58 S31-201 74 NVP-AEE 788 3,10,13 PI-103 53,57 SAHA 31 NVP-AUY922 69 PIK-293 55 Salbutamol sulfate 96 NVP-BEP800 69 PIK-75 HCl 57 SAR245408 54 NVP-BEZ235 54,57 PIK-90 55 Saracatinib 11 NVP-BHG712 7,12 PIK-93 55 SB 202190 49 NVP-LBH589 29 Pimobendan 95 SB 203580 49 NVP-TAE684 16 Piroxicam 78 SB 216763 57 Plinabulin 16 SB 431542 80 5 PLX-4032 50 SB 525334 16 PLX-4720 50 SB 743921 44 Obatoclax Mesylate 34 Pomalidomide 35 SB-715992 44 Oestriol 61 Ponatinib 6,11,12,16 SB939 31 Olaparib 38 Proscar 62 Secretin 105 Olmesartan 82 PT-141 103 Seliciclib 21 Olopatadine HCl 98 PXD101 29 Selumetinib 47 Omeprazole 86 Pyridostigmine Bromide 96 Selzentry 65 ON-01910 20 Pyroxamide 30 Semagacestat 72 Onxol 23 SEN0014196 31 Ornipressin 101 Serdemetan 35 OSI-420 6 7 SGX-523 15 OSI-930 8,14 Sildenafil citrate 95 Ostarine 60 Quercetin 12,55,76 Sirolimus 56 Oxymetazoline HCl 96 Sitagliptin phosphate 69 Oxytocin 100 8 SKF 89976A HCl 98 SKI-606 12 R406 17 SNS-032 22 6 R406(free base) 17 SNS-314 Mesylate 43 R788 17 Sodium valproate 31 Paclitaxel 23 RAD001 57 Somatostatin 105 Panobinostat 29 RAF265 8,50 Sophoretin 12,55,76 Papaverine HCl 95 Raltegravir 665 Sophoretin 55 Pazopanib HCl 8 Raltitrexed 24 Sorafenib Tosylate 9,50 PCI-24781 30 Ranitidine HCl 98 Sotalol HCl 83 PD0325901 48 Rapamycin 56 SP600125 50 PD0332991 21 Regorafenib 8,14,50 Sprycel 12 PD153035 HCl 4 Revlimid 35 STA-4783 68 PD173074 9,11,12 Reyataz 68 Stavudine 92 PD318088 48 RG7227 70 SU-11248 9 PD98059 48 Ritonavir 68 SU11274 15 Pelitinib 3 Rivaroxaban 91 SU6668 10 Pemetrexed disodium 24 RO4929097 72 Sulfamethoxazole 25 Perifosine 58 Roflumilast 94 Sunitinib Malate 9 PF-04217903 14 Rolipram 94 PF-2341066 14 Roscovitine 21 : PHA-665752 15 Rubex 22 PHA-680632 43 Tadalafil 95 TAK 165 6 Taltirelin 104 Veliparib 38 tamatinib fosdium 17 Vepesid 22 Tamoxifen Citrate 60 VER-82576 69 Tandutinib 15 Vicriviroc Malate 65 Tanespimycin 69 Vincristine Sulfate 23 Tarceva 4 Vinflunine 23 Tasigna 12 Vinflunine Tartrate 22 Tasosartan 82 Vinorelbine 49 Taxol 23 Vismodegib 72 Taxotere 23 Vorinostat 31 Telaprevir 70 VOTRIENT 8 Temsirolimus 56 VX-222 70 Tenofovir 92 VX-680 44 Tenofovir Disoproxil Fumarate 92 VX-702 49 Teriparatide 102 VX-745 49 Terlipressin 101 VX-770 85 TG100-115 55 VX-950 70 TGX-221 54 Tianeptine sodium 93 = Tivozanib 6 WYE-354 56 TKI-258 7 WZ3146 5 Tomudex 24 WZ4002 5 Topotecan HCl 22 WZ8040 5 Toremifene Citrate 60 Torisel 56 > Torisel 58 Tosedostat 70 XAV-939 72 Tovok 3,13 Xeloda 24 Tozasertib 44 XL147 54 Trichostatin A 31 XL184 9,16,17 Triptorelin 102 XL765 55,57 TSA 31 XL880 9,15 TSU-68 10 Xylazine 96 TW-37 34 Tykerb 3,13 ?

; Y-27632 20 YM155 35 U0126-EtOH 48 Ubenimex 70 UK-427857 65 @

< Zactima 5,10 Zalcitabine 93 Valproate Sodium 31 ZD-1839 3 Valsartan 82 ZD4054 16 Vandetanib 5,10 Zibotentan 16 Vapreotide 105 ZIP 103 Vardenafil 95 ZM 252868 4 Vargatef 10,11 ZM-447439 42 Vasopressin 101 Zolinza 31 Vatalanib 10 Zortress 57 Velcade 68 ZSTK474 55 View More Online www.selleckchem.com

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