New Products Spring and Summer 2017

Tree of Heaven Ailanthus altissima A Source of Ailanthone Products by Pharmacology • 7-TM Receptors • • Ion Channels Products for Cell Biology • Epigenetics • Fluorescent Imaging • Signal Transduction • Stem Cells New Products by Pharmacology

New Products – Spring and Summer 2017 Welcome to our New Product Guide, containing the latest additions to our product range over the last six months. Products are categorized by biological targets for easy identification, or simply browse the guide to see what is newly available. Our products are of the highest purity and full respect for third party intellectual property rights comes as standard. 7-TM Receptors 7-TM receptors are integral membrane proteins containing seven membrane-spanning helices that are coupled to G proteins on the intracellular face of the membrane. Upon binding, the undergoes a conformational change, activating the G protein and triggering signal transduction.

Category Cat. No. Product Name Description Unit Size Receptors

Antagonists 6137 8-Cyclopentyl-1,3-dimethylxanthine High affinity adenosine 1A receptor antagonist 100 mg

5965 ISAM 140 High affinity A2B receptor antagonist 10 mg 50 mg Calcium-Sensing Receptor Agonists 6170 Cinacalcet Calcium-sensing receptor (CaSR) allosteric agonist; also CYP2D2 10 mg inhibitor and Ca2+ channel blocker; orally bioavailable 50 mg Chemokine Receptors Antagonists 5872 AZ 10397767 Potent CXCR2 antagonist 10 mg 50 mg 5943 ML 339 Potent and selective hCXCR6 antagonist 10 mg 50 mg

Featured 7-TM Receptor Products HO

Cl OMe NH H OMe S O N N N H O N HN O OMe S N N H H O S N OH F ML 339 (5943) Cl ZQ 16 (6001) Potent and selective hCXCR6 antagonist Selective GPR84 agonist AZ 10397767 (5872) Potent CXCR2 antagonist

OMe O O2N HO HN O CO H O Cys-Arg-Pro-Arg-Leu-Cys-Lys-His-Cys-Arg- N 2 N Pro-Arg-Leu-Cys NO2 N N O NH2

Ro 6842262 (5913) MM 54 (5992) MDNI-caged-L-glutamate (5785) L Potent LPA1 antagonist Potent antagonist Stable photoreleaser of -glutamate

O O NC Cl OH O N O H H N O N N O H O N N S S O O F O O

ML 233 (5966) Ex 26 (5833) AZD 1283 (6085)

Non-peptide apelin receptor agonist Potent and selective S1P1 receptor antagonist High affinity antagonist

2 |

7-TM Receptors NEW PRODUCTS – spring and summer 2017

Category Cat. No. Product Name Description Unit Size Receptors

Agonists 6171 MLS 1547 G protein-biased D2 receptor partial agonist 10 mg 50 mg Free Fatty Acid Receptors Agonists 5789 AM 4668 Potent FFA1 (GPR40) agonist 10 mg 50 mg 6001 ZQ 16 Selective GPR84 agonist 10 mg 50 mg 6082 AMG 837 hemicalcium salt Potent FFA1 (GPR40) partial agonist 10 mg 50 mg Antagonists 5903 CATPB FFA2 antagonist/inverse agonist 10 mg 50 mg

GABAB Ligands 5518 UMB 68 GHB receptor ligand 10 mg 50 mg Glutamate (Metabotropic) Receptors

Modulators 5362 TASP 0433864 Selective mGlu2 receptor positive allosteric modulator 10 mg 50 mg Other 5785 MDNI-caged-l-glutamate Stable photoreleaser of l-glutamate 10 mg GPBA Receptors Agonists 6026 Oleanolic acid Selective GPBA receptor (TGR5) partial agonist 50 mg Receptors

Antagonists 5913 Ro 6842262 Potent LPA1 antagonist 10 mg 50 mg Opioid Receptors Modulators 5983 BMS 986187 Potent δ- positive allosteric modulator 10 mg 50 mg Peptide Receptors Agonists 6030 Amylin (rat) Potent endogenous peptide agonist for amylin, , CGRP 500 µg and adrenomedullin receptors

5488 BML 111 FPR2 (lipoxin A4 receptor) agonist 10 mg 6031 Calcitonin (human) Endogenous agonist; inhibits bone resorption 500 µg 5966 ML 233 Non-peptide apelin receptor agonist 10 mg 50 mg

6090 Spexin Potent GAL2/3 agonist; exhibits anxiolytic effects in vivo 1 mg

Antagonists 6232 Bosentan High affinity dual ETA and ETB receptor antagonist; orally 10 mg bioavailable 50 mg 5992 MM 54 Potent apelin receptor antagonist 1 mg

5954 MSG 606 Potent human MC1 receptor antagonist; also MC3 and MC5 1 mg partial agonist Prostanoid Receptors

Antagonists 5701 AMG 853 Potent dual CRTH2 and prostaglandin D2 (PGD2) receptor 10 mg antagonist Purinergic (P2Y) Receptors

Antagonists 5720 AR-C 69931 tetrasodium salt Highly potent P2Y12 antagonist 1 mg

6085 AZD 1283 High affinity P2Y12 antagonist 10 mg 50 mg Sphingosine Receptors Agonists 6176 FTY 720 Potent S1P receptor agonist; also immunosuppressant 10 mg 50 mg

Antagonists 5833 Ex 26 Potent and selective S1P1 receptor antagonist 10 mg 50 mg

tocris.com | 3 New Products by Pharmacology Enzymes Enzymes are proteins that catalyze a chemical change in a substrate. Some enzymes act independently, but others require the assistance of coenzymes or cofactors in order to function correctly. Enzymes can be classified into numerous groups according to their substrate or the type of chemical reaction they catalyze.

Category Cat. No. Product Name Description Unit Size ATPases/GTPases Inhibitors 5986 NAV 2729 Selective ARF6 inhibitor 10 mg 50 mg Cyclases Activators 5708 BAY 41-8543 Increases activity of guanylyl cyclase (sGC) stimulator 10 mg 50 mg 6052 BAY 58-2667 Potent soluble guanylyl cyclase (sGC) activator 10 mg Cytochrome P450 Inhibitors 6108 Galeterone CYP17 inhibitor; also androgen receptor antagonist 10 mg 50 mg Substrates 6204 7-Ethoxyresorufin Fluorometric CYP450 substrate 10 mg Dehydrogenases Inhibitors 5934 NCT 501 Potent and selective ALDH1A1 inhibitor 10 mg 50 mg Hydrolases Inhibitors 5952 PDD 00017273 Potent and selective poly (ADP ribose) glycohydrolase (PARG) 10 mg inhibitor; cell permeable Isomerases Inhibitors 5125 CKD 602 Topoisomerase I inhibitor 10 mg 50 mg Kinases Activators 6034 AM 2394 Potent glucokinase activator; orally bioavailable 10 mg 50 mg 6114 PF 06409577 Potent and selective allosteric activator of AMPK 10 mg 50 mg

Featured Products

N

Cl O S O N O N N N N N N OH O HN N N O

N OH

O O N NCT 501 (5934) BAY 58-2667 (6052) FRAX 597 (6029) Potent and selective ALDH1A1 inhibitor Potent soluble guanylyl cyclase activator Potent group I PAK inhibitor N

O N O O O HO S S N N N HN N H H2N H N N 2 N N O N O N O H O O N N N O N N

PDD 00017273 (5952) AM 2394 (6034) eCF 309 (5955) Potent and selective poly (ADP ribose) Potent glucokinase activator; Potent mTOR inhibitor glycohydrolase (PARG) inhibitor orally bioavailable

4 |

O

O H N H N N N N N N N H N N O N N S N H O

PF 04449613 (5915) PF 3758309 (6005) Potent PDE9 inhibitor; brain penetrant Potent PAK4 inhibitor; orally available

O NH2 S O N 2 O O HN N S O N O

S S O

CCF 642 (6063) PF 06281355 (6004) Protein disulfide isomerase (PDI) inhibitor Selective myeloperoxidase (MPO) inhibitor; orally bioavailable

Enzymes NEW PRODUCTS – spring and summer 2017

Category Cat. No. Product Name Description Unit Size Inhibitors 5955 eCF 309 Potent mTOR inhibitor 10 mg 50 mg 6029 FRAX 597 Potent group I PAK inhibitor 10 mg 50 mg 5632 AZ Dyrk1B 33 Potent and selective Dyrk1B kinase inhibitor 10 mg 5742 AZ PFKFB3 67 Potent and selective PFKFB3 inhibitor 10 mg 50 mg 6071 CZC 25146 Potent LRRK2 inhibitor 10 mg 50 mg 5834 LTURM 34 Potent DNA-PK inhibitor 10 mg 50 mg 5756 MLi-2 Potent and selective LRRK2 inhibitor 10 mg 50 mg 6005 PF 3758309 Potent PAK4 inhibitor; orally available 10 mg 50 mg 4546 rac-CCT 250863 Potent Nek2 inhibitor 5 mg 6015 RAF 265 Raf kinase and VEGFR-2 inhibitor 10 mg 50 mg 5909 RMM 46 MSK/RSK family kinase inhibitor 10 mg 50 mg 5968 Ro 3280 Potent and selective PLK1 inhibitor 10 mg 50 mg 5570 STOCK2S 26016 Lysine deficient protein kinase (WNK) signaling inhibitor 10 mg 50 mg Lipases Inhibitors 5851 JZP 361 Potent and selective reversible MAGL inhibitor 10 mg 50 mg 6020 URB 602 Non-competitive MAGL inhibitor 10 mg 50 mg

New Compound Libraries

Tocris has launched a range of new compound libraries composed of biologically active molecules that have proven pharmacological activity against a wide range of targets. Use them in your phenotypic screening studies, drug repurposing campaigns or for validation of new molecular targets. Compounds are supplied pre-dissolved in DMSO, and full chemical and biological data are available. All compounds have the same proven solubility, purity and stability as all those in the Tocris catalog.

Tocriscreen Plus (Cat. No. 5840) A unique library of 1280 biologically active compounds, with many exclusive to Tocris (250 mL 10 mM DMSO solutions)

Tocriscreen Library of FDA Approved Compounds (Cat. No. 5932) A library of 160 FDA-approved compounds (250 mL 10 mM DMSO solutions)

Tocris also has available single plate Toolboxes for Kinase Inhibitors, Stem Cells and Epigenetics

For more information visit www.tocris.com/tocriscreen

tocris.com | 5 New Products by Pharmacology Enzymes – continued

Category Cat. No. Product Name Description Unit Size Lyases Inhibitors 6101 SHIP 2a Cystathione γ lyase (CSE) inhibitor 10 mg 50 mg Oxygenases N Inhibitors 6004 PF 06281355 Selective myeloperoxidase (MPO) inhibitor 10 mg Cl O S 50 mg O Phosphatases N O N N Inhibitors 5724 NQ 301 Selective CD45 inhibitor 10 mg N N N N OH O HN N N O 50 mg Phosphodiesterases N Inhibitors 5695 Eggmanone Potent and selective PDE4OH inhibitor; suppresses hedgehog 10 mg O signaling 50 mg O 5915 PF 04449613 Potent PDE9 inhibitor; brain penetrant N 10 mg NCT 501 (5934) BAY 58-2667 (6052) FRAX 597 (6029) Polymerases Potent and selective ALDH1A1 inhibitor Potent soluble guanylyl cyclase activator Potent group I PAK inhibitor Inhibitors 5312 BRACO 19 Telomerase inhibitor N 10 mg 50 mg Proteases 6033 ( )-MG 132 PotentO 20S proteasomeN inhibitor 10 mg Inhibitors O O R O HO 6019S Diprotin A S Dipeptidyl peptidase IV (DPP-IV) inhibitor 10 mg N N N HN N 6088H SB 3CT Selective high affinity MMP2 inhibitor H2N 10 mg H N N 2 N N O N Reductases O N O H O 6063 CCF 642 Protein disulfide isomerase (PDI) inhibitor O 10 mg Inhibitors N N N 50O mg N N Synthases/Synthetases Inhibitors 5791PDD 00017273Bz 423 (5952) ATP synthaseAM 2394 inhibitor; (6034) proapoptotic eCF 309 (5955) 10 mg Potent and selective poly (ADP ribose) Potent glucokinase activator; Potent mTOR inhibitor 50 mg gl6111ycohydrolaseZoledronic (PARG) Acidinhibitor Potento rfarnesylally bio adiphosphatevailable (FPP) synthase inhibitor 10 mg 50 mg Transferases Inhibitors 5762 BMS 795311 Potent cholesteryl ester transfer protein (CETP) inhibitor 10 mg

Featured Enzyme Products (continued)

O

O H N H N N N N N N N H N N O N N S N H O

PF 04449613 (5915) PF 3758309 (6005) Potent PDE9 inhibitor; brain penetrant Potent PAK4 inhibitor; orally available

O NH2 S O N 2 O O HN N S O N O

S S O

CCF 642 (6063) PF 06281355 (6004) Protein disulfide isomerase (PDI) inhibitor Selective myeloperoxidase (MPO) inhibitor; orally bioavailable

Enzymes

6 | NEW PRODUCTS – spring and summer 2017 Enzyme-Linked Receptors Enzyme-linked receptors are a group of multi-subunit transmembrane proteins that contain either intrinsic enzyme activity on their intracellular domain, or associate directly with an intracellular enzyme. Upon ligand binding, a conformational change is transmitted via a transmembrane helix. This activates the enzyme, initiating signaling cascades.

Category Cat. No. Product Name Description Unit Size Integrins Inhibitors 6058 ATN 161 α5β1 integrin receptor antagonist 10 mg MET Receptors Inhibitors 6056 GSK 1363089 Potent inhibitor of MET, VEGFR2, Ron and AXL 10 mg 50 mg Receptor Tyrosine Kinases (RTKs) Inhibitors 5993 CP 673451 Potent and selective PDGFR inhibitor 10 mg 6115 PF 06273340 Potent and selective pan-Trk inhibitor; peripherally restricted 10 mg Toll-like Receptors Agonists 6011 FSL 1 TLR2/6 agonist (also a putative TLR10 ligand) 100 µg

Featured Enzyme-Linked Receptor Products N Cl

HN O O NH2 N N N N N H2N N N N O O OH

CP 673451 (5993) PF 06273340 (6115) Potent and selective PDGFR inhibitor Potent and selective pan-Trk inhibitor; peripherally restricted

Licensing at Tocris

Tocris Bioscience has a long tradition of workingEnzym ewith-Linked scientists Recep totors bring new discoveries out of the laboratory and into the commercial arena. We work in partnership with many scientists within both universities and pharmaceutical companies to bring life science tools to the global research community. Tocris' policy has always been to never knowingly infringe third party intellectual property. It is our intention to remain a responsible and ethical supplier, and work with the scientific community. Our Expertise Our licensing department has significant experience of drafting contracts and has successfully executed licenses with a multitude of licensors, including: • Large pharmaceutical companies • Start-up/spin-out companies • University technology transfer offices • Individual researchers Contact Us To discuss licensing opportunities, please contact our licensing team at [email protected]

tocris.com | 7 New Products by Pharmacology Ion Channels Ion channels are pore-forming membrane proteins that allow the passage of ions across the plasma membrane. Hundreds of different ion channels have been identified in the membranes of all mammalian cells; they can be broadly classified by different properties including the gating mechanism (e.g. voltage or ligand) or ion selectivity of their pore.

Category Cat. No. Product Name Description Unit Size Calcium Channels Other 6210 ci-IP3/PM Caged inositol triphosphate 10 µg Chloride Channels Blockers 6076 Ani 9 Potent and selective TMEM16A (Anoctamin‑1; ANO1) blocker 10 mg 50 mg 5770 MONNA Potent TMEM16A (Anoctamin‑1) blocker 10 mg 50 mg Glutamate (Ionotropic) Receptors Other 5996 (R)-Norketamine NMDA ; analgesic 10 mg 6112 (S)-Norketamine NMDA receptor modulator; analgesic 10 mg 6094 2R,6R-Hydroxynorketamine Enhances AMPA currents; decreases d- (a NMDA 10 mg co‑agonist); lacks ketamine-related side effects 6095 2S,6S-Hydroxynorketamine Decreases d-serine (a NMDA co-agonist); antidepressant 10 mg Potassium Channels

Activators 6233 Retigabine KV7 channel activator 10 mg 50 mg

Blockers 6086 AMP PNP Kir6 (KATP) channel blocker; non-hydrolyzable AMP analog 10 mg Sodium Channels

Blockers 6159 4,9-Anhydrotetrodotoxin Potent and selective NaV1.6 channel blocker 100 µg Transient Receptor Potential Channels Antagonists 5995 AMG 517 Potent TRPV1 antagonist 10 mg 50 mg Blockers 6003 PF 05105679 Selective TRPM8 blocker 10 mg

Featured Ion Channels Products

.HCl O O NH NH2 2 ci-IP3/PM (6210) O O HO Caged inositol triphosphate O O O Cl Cl O O P O O O 2S,6S-Hydroxynorketamine (6095) (R)-Norketamine (5996) O NO2 Decreases D-serine (a NMDA co-agonist); O O NMDA receptor modulator P antidepressant O O O O O O P O O O O O O O O O O NH2 NH2 HO O O Cl Cl 2R,6R-Hydroxynorketamine (6094) O OH (S)-Norketamine (6112) Enhances AMPA currents; decreases D-serine NMDA receptor modulator (a NMDA co-agonist); lacks ketamine-related side effects

N

O N

NO2 O

N H

HO O F

MONNA (5770) PF 05105679 (6003) Potent TMEM16A (Anoctamin-1) blocker Selective TRPM8 blocker; orally bioavailable

8 |

Ion Channels NEW PRODUCTS – spring and summer 2017 Nuclear Receptors Nuclear receptors (also known as nuclear hormone receptors) are a large family of transcription factors that bind directly to DNA to regulate the expression of target genes. They regulate the cellular response to hormones such as sex steroids,

vitamin D3, adrenal steroids and other metabolic ligands, and are involved in metabolism, development and reproduction.

Category Cat. No. Product Name Description Unit Size LXR-Like Receptors Agonists 6138 SR 9234 LXR inverse agonist 10 mg 50 mg Retinoic Acid Receptors Antagonists 5758 AGN 193109 Potent retinoic acid receptor (RAR) antagonist 10 mg

Transporters Transporters are specialized membrane-spanning proteins that aid the movement of ions, peptides, small molecules, lipids and macromolecules across a lipid bilayer. There are three main classes of transporter: ABC transporters, P-type ATPases and the solute carrier family. Transporters can move substances either actively or passively.

Category Cat. No. Product Name Description Unit Size Na+/Ca2+ Exchanger Inhibitors 5692 ITH 12575 Mitochondrial Na+/Ca2+ exchange (mNCX) inhibitor. 10 mg 50 mg Transporters Inhibitors 6131 (R)-Modafinil Dopamine uptake inhibitor 10 mg 50 mg 4447 Org 24598 Inhibitor of GlyT1; derivative of Org 24598 lithium salt 10 mg (Cat. No. 4035). 50 mg

Mitochondrial Na+/Ca2+ exchange inhibitor ITH 12575 Cat. No. 5692 ITH 12575 is a mitochondrial Na+/Ca2+ exchange (mNCX) inhibitor. The compound reduces Ca2+ efflux from the mitochondria to the cytosol in HeLa cells S (EC50 = 0.69 μM). ITH 12575 also protects against glutamate-induced Cl excitotoxicity in rat hippocampal slices and oligomycin A/rotenone-induced

N oxidative stress in neuroblastoma cells in vitro. H O

ITH 12575 (5692)

ITH 12575 is a mitochondrial Na+/Ca2+ exchange (mNCX) inhibitor. The compound reduces Ca2+ afflux from the mitochondria to the cytosol in HeLa cells (EC50 = 0.69 µM). 12575 also protects against glutamate-induced excitotoxitiy in rat hippocampal slices and oligomycin A/rotenone-induced oxidative stress in neuroblastoma cells in vitro.

Transporters

tocris.com | 9 New Products for Cell Biology Apoptosis Apoptosis is a form of programmed cell death that involves caspase-dependent intracellular signaling, resulting in phagocytosis of unwanted cells. The cell cycle is a regulatory network that controls cell proliferation and detects DNA damage. In the event that DNA damage cannot be repaired, the cell is destroyed through apoptotic mechanisms.

Category Cat. No. Product Name Description Unit Size Apoptosis Inducers Other 5804 Chaetoglobosin A Selectively induces apoptosis of CLL cells; antibiotic 1 mg

Cell Metabolism Cellular metabolism describes a set of chemical reactions that occur in living organisms in order to maintain life. Cellular metabolism involves complex sequences of controlled biochemical reactions, better known as metabolic pathways. These processes allow organisms to grow and reproduce, maintain their structures, and respond to environmental changes.

Category Cat. No. Product Name Description Unit Size Autophagy Inhibitors 5780 MRT 68921 Potent ULK inhibitor; inhibits autophagy 10 mg 50 mg DNA, RNA and Protein Synthesis Inhibitors 5962 3-AP Ribonucleotide reductase inhibitor; also an iron chelator 10 mg 50 mg 6070 Pladienolide B mRNA splicing inhibitor; antitumor 500 µg 5419 PCNA I1 Proliferating cell nuclear antigen (PCNA) inhibitor 10 mg 50 mg Lipid Metabolism Inhibitors 5850 HM 50316 High affinity FABP4 inhibitor 10 mg 50 mg Neuronal Metabolism Other 6250 Filipin III Polyene antibiotic; inhibits formation of pathological isoform of 1 mg prion protein

Potent ULK inhibitor MRT 68921 Cat. No. 5780

H H H MRT 68921 is a potent ULK inhibitor (IC values are 1.1 and 2.9 nM for N N N N 50 ULK2 and ULK1, respectively). The compound inhibits autophagy in mouse N N O embryonic fibroblasts

MRT 68921 (5780) Potent ULK inhibitor

MRT 68921 is a potent ULK inhibitor (IC50 values are 1.1 and 2.9 nM for ULK2 and ULK1, respectively). The compound inhibits autophagy in mouse embryonic fibroblasts

Cell Metabolism

10 | NEW PRODUCTS – spring and summer 2017 Epigenetics Epigenetics is the study of acquired changes or modifications in chromatin structure that arise independently of a change in the underlying DNA nucleotide sequence. Epigenetic modifications alter the accessibility of DNA to transcription machinery, thereby influencing gene expression.

Category Cat. No. Product Name Description Unit Size Bromodomains Inhibitors 5970 BAY 299 Potent and selective BRD1 and TAF1 inhibitor 10 mg 50 mg 6000 TP 472 Potent BRD9/7 inhibitor 10 mg Other 5999 TP 472N Negative control for TP 472 (Cat. No. 6000) 10 mg Histone Deacetylases Inhibitors 6010 BRD 4354 HDAC5 and HDAC9 inhibitor 10 mg 50 mg 6124 (R)-2-Hydroxyglutaric acid KDM4A inhibitor; oncometabolite produced by mutant IDH1 50 mg disodium salt and 2; also NF-κB activator Lysine Methyltransferase Inhibitors 6169 PF 06726304 Highly potent and SAM-competitive EZH2 inhibitor 10 mg PROTACs Other 6154 MZ 1 (+)-JQ1 based PROTAC that selectively degrades BRD4 in cells 5 mg 6155 cis MZ 1 Negative control for MZ 1 (Cat. No. 6154) 5 mg Protein Arginine Methyltransferases Inhibitors 6008 TP 064 Potent and selective PRMT4 inhibitor 10 mg 50 mg 5777 GSK 591 Potent and selective PRMT5 inhibitor 10 mg

PROTACs – New from Tocris MZ 1 (#6154) is a PROTAC (PROteolysis TArgeting Chimera), a new tool for epigenetics research from Tocris. PROTACs are bifunctional small molecules, comprising binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, that harness the ubiquitin/proteasome system (UPS) to selectively remove target proteins from cells.

Key features of MZ 1 How PROTACs Work: Schematic showing PROTACs catalytic mode of • Selectively induces degradation of BRD4 by the action. PROTACs allow the formation of a ternary complex between E3 proteasome ubiquitin ligase and a target protein which results in polyubiquitination • Catalytic mode of action of the target protein, its recognition by the proteasome and subsequent • Negative control, cis MZ 1 (#6155), also available degradation. PROTACs act catalytically by repeatedly engaging and directing the ubiquitination of target molecules. (Adapted from • Licensed from Alessio Ciulli at the University of Timworth et al. (2016) Med.Chem.Comm. 7 2206) Dundee (UK)

Ub Ub NH2 PROTAC NH2 E2 E2

Ternary E3 ligase E3 ligase complex

Target Protein Catalytic – PROTAC is recycled

Ub Ub Ub Ub

NH2

Peptide fragments Proteasome Polyubiquitination

tocris.com | 11 New Products for Cell Biology Fluorescent Imaging Fluorescent probes and dyes facilitate the visualization of subcellular components in live and fixed cells with high sensitivity and selectivity and enable monitoring of dynamic intracellular biochemical reactions. Fluorescent dyes may also be conjugated to antibodies for immunohistochemistry and flow cytometry use.

Category Cat. No. Product Name Description Unit Size Fluorescent Imaging Other 6065 2-NBDG Fluorescent glucose uptake indicator 5 mg 5436 Cyanine 5, SE Red fluorescent dye for the labeling of amines 10 mg 5824 Hoechst 33258 Fluorescent dye for labeling DNA 50 mg 6147 Janelia Fluor™ 549, SE Cell permeable fluorescent dye; supplied as NHS ester 5 mg 6148 Janelia Fluor™ 646, SE Cell permeable fluorescent dye; supplied as NHS ester 5 mg 5911 FFN 200 Fluorescent VMAT2 substrate 10 mg 5561 IHR-Cy3 Potent fluorescent Smo antagonist 1 mg 6046 Naloxone fluorescein acetate Fluorescent opioid antagonist; fluorescent-derivative of naloxone 100 µg (Cat. No. 0599)

Featured Fluorescent Imaging Products

NH2 N O N+

- CO2 O H2N O O O N FFN 200 (5911) Cl NH O Selective fluorescent VMAT2 substrate O O O NH Janelia FluorTM 549, SE (6147) Fluorescent dye; supplied as an NHS ester for coupling to primary amine groups; compatible with self-labeling O tag systems Cl NH HN O + N Si N Cl

- CO2 O Et + O N N N O O

- SO3H O S Janelia FluorTM 646, SE (6148) 3 Fluorescent dye; supplied as an NHS ester for coupling IHR-Cy3 (5561) to primary amine groups; compatible with self-labeling Potent fluorescent Smo antagonist tag systems

Fluorescent Imaging

12 | NEW PRODUCTS – spring and summer 2017 Signal Transduction Signal transduction, or intracellular signaling, is the transmission of molecular signals from a cell’s exterior to its interior. This process is initiated by cell surface receptors, and is required to ensure an appropriate cellular response. Signal transmission is propagated by either biochemical changes within the cell, or by membrane potential alterations.

Category Cat. No. Product Name Description Unit Size

Cytokine and NF-κB Signaling Inhibitors 5846 IT 901 NF-κB c-Rel subunit inhibitor 10 mg 50 mg 4238 PF 184 Potent and selective IKKβ inhibitor 10 mg 5300 BI 605906 Selective IKKβ inhibitor 10 mg 6107 CP 424174 Inhibitor of IL-1β post-translational processing; indirectly 10 mg inhibits NLRP3 50 mg 5672 GSK 319347A Potent and selective IKKε inhibitor 10 mg G Proteins (small) Inhibitors 6025 (S)-Crizotinib MTH1 inhibitor 10 mg 50 mg Hedgehog Signaling Activators 5282 SAG 21k Hedgehog signaling activator; brain penetrant and orally 10 mg bioavailable MAPK Signaling Inhibitors 5843 AX 15836 Potent and selective ERK5 inhibitor 10 mg 6014 Org 48762-0 Selective p38α/β inhibitor; orally bioavailable 10 mg 50 mg NO Donors/Precursors Other 6077 DETA NONOate donor 10 mg PI 3-K/Akt Signaling Inhibitors 5835 LTURM 36 PI 3-kinase δ inhibitor 10 mg 50 mg

6087 Perifosine PKB/Akt inhibitor; also modulates KV2.1 current 10 mg 50 mg 5919 PI 3065 Potent and selective PI 3-kinase p110δ inhibitor 10 mg 50 mg

Featured Signal Transduction Products

N S N CN Cl O N O MeO S N O O NH F MeO Cl H2N N O N N GSK 319347A (5672) (S)-Crizotinib (6025) Potent and selective IKKε inhibitor Potent MTH1 inhibitor HN N N EtO S O O O H N O O O N N N N

NH2 HCl N

AMBMP (6043) AX 15836 (5843) Wnt canonical signaling activator; Potent and selective ERK5 inhibitor also inhibits tubulin polymerization.

Signal Transduction tocris.com | 13 New Products for Cell Biology Signal transduction – continued

Category Cat. No. Product Name Description Unit Size Transcription Factors Other 5761 RG 102240 Gene switch ligand for use in inducible gene expression systems 10 mg 50 mg Translocation, Exocytosis & Endocytosis Other 5978 WL 47 - dimer High affinity caveolin-1 ligand 1 mg Wnt Signaling Activators 6043 AMBMP Wnt canonical signaling activator; also tubulin polymerization 10 mg inhibitor 50 mg Inhibitors 5813 NSC 668036 Wnt signaling inhibitor; binds the PDZ domain of the Dishevelled 10 mg (Dvl) protein 50 mg

Reagents Our wide and expanding range of research reagents includes biochemicals, buffers, solvents, labels and stains, as well as stable isotopically labeled compounds.

Category Cat. No. Product Name Description Unit Size Reagents Other 6117 CORM 2 -releasing molecule 100 mg 5407 GA3-AM Chemical dimerizer; cell permeable 10 mg 50 mg 4991 HaXS8 Chemical dimerizer 2 mg 6146 LAP Photocrosslinker for hydrogels 500 mg

Chemical dimerizer; cell permeable HaXS8 Cat. No. 4991 N O

HN N N HaXS8 is a cell permeable chemical dimerizer that promotes covalent and F F NH2 NH irreversible HaloTag™ and SNAP-tag™ substrate dimerization (HaloTag Cl is a trademark of Promega Corporation, and SNAP-tag is a trademark of O O O New England BioLabs, Inc.)

O F F O O O

HaXS8 (4991) Chemical dimerizer; cell permeable

HaXS8 is a cell permeable chemical dimerizer that promotes covalent and irreversible HaloTag™ and SNAP-tag™ substrate dimerization (HaloTag is a trademark of Promega Corporation, and SNAP-tag is a trademark of New England BioLabs, Inc.)

Reagents

14 | NEW PRODUCTS – spring and summer 2017 Stem Cells Stem cells are pluripotent or multipotent cells that are capable of self-renewal through mitotic cell division, and which may be induced to form more specialized cells of a tissue or organ by a process termed cellular differentiation. Key morphogens, such as Wnt, Hedgehog and Notch, influence stem cell self-renewal and differentiation.

Category Cat. No. Product Name Description Unit Size Reprogramming Other 6044 AS 8351 Induces reprogramming of fibroblasts into functional 10 mg cardiomyocytes 50 mg 6066 OAC-2 Oct4 activator; enhances iPSC reprogramming efficiency 10 mg 50 mg Stem Cell Differentiation Other 6053 LDN 193189 Potent and selective ALK2 and ALK3 inhibitor; promotes neural 10 mg induction of hPSCs 50 mg 6068 Lin28 1632 RNA binding protein Lin28 inhibitor; promotes mESC 10 mg differentiation; also bromodomain inhibitor 50 mg Stem Cell Proliferation Other 5779 NSC 23005 sodium Potently promotes HSC expansion; p18INK inhibitor 10 mg 50 mg

Featured Stem Cells Products

HN

N N N N N N O N N

LDN 193189 (6053) N Lin28 1632 (6068) Promotes neural induction Induces differentiation of murine ESCs and of hPSCs; potent and selective inhibits stemness; RNA binding protein Lin28 ALK2 and ALK3 inhibitor inhibitor; also bromodomain inhibitor N

Life Science Literature from Tocris Stem Cells Tocris also provides a wide range of scientific literature free of charge, including the following titles:

Product Guides & Listings Life Science Posters Scientific Reviews

• GPCRs • Vascular Reactivity • Ras Oncoproteins • Kinases • Gut Hormones • Nicotinic ACh Receptors • Cancer Research • Cancer Metabolism • Dopamine Receptors • Neurodegeneration • Addiction • Stem Cells

To download or request copies, please visit www.tocris.com/requestliterature

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