new products - tocris bioscience · pdf filenew products tree of heaven ailanthus altissima...
TRANSCRIPT
New Products
Tree of HeavenAilanthus altissimaA Source of Ailanthone
Products by Pharmacology• 7-TM Receptors• Enzymes• Ion Channels
Products for Cell Biology• Epigenetics• Fluorescent Imaging• Signal Transduction• Stem Cells
Spring and Summer 2017 | Euro
New Products by Pharmacology
2 |
7-TM Receptors7-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 ligand binding, the receptor undergoes a conformational change, activating the G protein and triggering signal transduction.
New Products – Spring and Summer 2017Welcome 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
HO
NH
SO
NHNS
F
Cl
N
AZ 10397767 (5872)Potent CXCR2 antagonist
HNN
O
HN
Cl
O
OMe
OMe
OMe
H
ML 339 (5943)Potent and selective hCXCR6 antagonist
S N OH
O
HN
ZQ 16 (6001)Selective GPR84 agonist
OMe
NO2
N
O
CO2H
NH2
O2N
MDNI-caged-L-glutamate (5785)Stable photoreleaser of L-glutamate
N N
N
HN O
O
HO
O
Ro 6842262 (5913)Potent LPA1 antagonist
O
NO
SO O
ML 233 (5966)Non-peptide apelin receptor agonist
Cys-Arg-Pro-Arg-Leu-Cys-Lys-His-Cys-Arg-Pro-Arg-Leu-Cys
MM 54 (5992)Potent apelin receptor antagonist
O
O
NC
NN
O
HN
SO
O
AZD 1283 (6085)High affinity P2Y12 antagonist
HN
F
O
NH
OH
O
Cl
Ex 26 (5833)Potent and selective S1P1 receptor antagonist
Featured 7-TM Receptor Products
Adenosine Receptors
Antagonists 6137 8-Cyclopentyl-1,3-dimethylxanthine High affinity adenosine A1 receptor antagonist 100 mg 130
5965 ISAM 140 High affinity A2B receptor antagonist 10 mg
50 mg
175
680
Calcium-Sensing Receptor
Agonists 6170 Cinacalcet Calcium-sensing receptor (CaSR) allosteric agonist; also CYP2D2 inhibitor and Ca2+ channel blocker; orally bioavailable
10 mg
50 mg
100
370
Chemokine Receptors
Antagonists 5872 AZ 10397767 Potent CXCR2 antagonist 10 mg
50 mg
210
835
5943 ML 339 Potent and selective hCXCR6 antagonist 10 mg
50 mg
140
505
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 3
Dopamine Receptors
Agonists 6171 MLS 1547 G protein-biased D2 receptor partial agonist 10 mg
50 mg
140
520
Free Fatty Acid Receptors
Agonists 5789 AM 4668 Potent FFA1 (GPR40) agonist 10 mg
50 mg
195
760
6001 ZQ 16 Selective GPR84 agonist 10 mg
50 mg
140
505
6082 AMG 837 hemicalcium salt Potent FFA1 (GPR40) partial agonist 10 mg
50 mg
195
760
Antagonists 5903 CATPB FFA2 antagonist/inverse agonist 10 mg
50 mg
160
630
GABAB
Ligands 5518 UMB 68 GHB receptor ligand 10 mg
50 mg
70
255
Glutamate (Metabotropic) Receptors
Modulators 5362 TASP 0433864 Selective mGlu2 receptor positive allosteric modulator 10 mg
50 mg
190
740
Other 5785 MDNI-caged-l-glutamate Stable photoreleaser of l-glutamate 10 mg 285
GPBA Receptors
Agonists 6026 Oleanolic acid Selective GPBA receptor (TGR5) partial agonist 50 mg 70
Lysophosphatidic Acid Receptors
Antagonists 5913 Ro 6842262 Potent LPA1 antagonist 10 mg
50 mg
210
820
Opioid Receptors
Modulators 5983 BMS 986187 Potent δ-opioid receptor positive allosteric modulator 10 mg
50 mg
180
705
Peptide Receptors
Agonists 6030 Amylin (rat) Potent endogenous peptide agonist for amylin, calcitonin, CGRP and adrenomedullin receptors
500 µg 240
5488 BML 111 FPR2 (lipoxin A4 receptor) agonist 10 mg 175
6031 Calcitonin (human) Endogenous calcitonin receptor agonist; inhibits bone resorption 500 µg 225
5966 ML 233 Non-peptide apelin receptor agonist 10 mg
50 mg
165
635
6090 Spexin Potent GAL2/3 agonist; exhibits anxiolytic effects in vivo 1 mg 210
Antagonists 6232 Bosentan High affinity dual ETA and ETB receptor antagonist; orally bioavailable
10 mg
50 mg
80
275
5992 MM 54 Potent apelin receptor antagonist 1 mg 245
5954 MSG 606 Potent human MC1 receptor antagonist; also MC3 and MC5 partial agonist
1 mg 245
Prostanoid Receptors
Antagonists 5701 AMG 853 Potent dual CRTH2 and prostaglandin D2 (PGD2) receptor antagonist
10 mg 275
Purinergic (P2Y) Receptors
Antagonists 5720 AR-C 69931 tetrasodium salt Highly potent P2Y12 antagonist 1 mg 230
6085 AZD 1283 High affinity P2Y12 antagonist 10 mg
50 mg
145
545
Sphingosine Receptors
Agonists 6176 FTY 720 Potent S1P receptor agonist; also immunosuppressant 10 mg
50 mg
95
355
Antagonists 5833 Ex 26 Potent and selective S1P1 receptor antagonist 10 mg
50 mg
165
635
Category Cat. No. Product Name Description Unit Size Euro
New Products by Pharmacology
4 |
EnzymesEnzymes 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.
Enzymes
N
N
N
O
N
O
N
O N
NCT 501 (5934)Potent and selective ALDH1A1 inhibitor
N
N
O
O
SNH
OO
N
S
N N
PDD 00017273 (5952)Potent and selective poly (ADP ribose)
glycohydrolase (PARG) inhibitor
N
NH
O
HN
O
N
NOHO
AM 2394 (6034)Potent glucokinase activator;
orally bioavailable
N
N
N NO
O
H2NN
O
H2N
eCF 309 (5955)Potent mTOR inhibitor
NNH
O
N
NH
N
HN
S
N
N
PF 3758309 (6005)Potent PAK4 inhibitor; orally available
O
O
O
HN
S
N
NH2O
PF 06281355 (6004)Selective myeloperoxidase (MPO)
inhibitor; orally bioavailable
O
N
SS
S
O2N
O
CCF 642 (6063)Protein disulfide isomerase (PDI) inhibitor
OH
O
N
O
OH
O
BAY 58-2667 (6052)Potent soluble guanylyl cyclase activator
HN
N
N
N
N
N O
ClS
N
FRAX 597 (6029)Potent group I PAK inhibitor
N
O N
O
HN N
N
O
PF 04449613 (5915)Potent PDE9 inhibitor; brain penetrant
Featured Enzyme Products
ATPases/GTPases
Inhibitors 5986 NAV 2729 Selective ARF6 inhibitor 10 mg
50 mg
180
705
Cyclases
Activators 5708 BAY 41-8543 Increases activity of guanylyl cyclase (sGC) stimulator 10 mg
50 mg
210
820
6052 BAY 58-2667 Potent soluble guanylyl cyclase (sGC) activator 10 mg 210
Cytochrome P450
Inhibitors 6108 Galeterone CYP17 inhibitor; also androgen receptor antagonist 10 mg
50 mg
145
560
Substrates 6204 7-Ethoxyresorufin Fluorometric CYP450 substrate 10 mg 165
Dehydrogenases
Inhibitors 5934 NCT 501 Potent and selective ALDH1A1 inhibitor 10 mg
50 mg
260
1030
Hydrolases
Inhibitors 5952 PDD 00017273 Potent and selective poly (ADP ribose) glycohydrolase (PARG) inhibitor; cell permeable
10 mg 270
Isomerases
Inhibitors 5125 CKD 602 Topoisomerase I inhibitor 10 mg
50 mg
70
255
Kinases
Activators 6034 AM 2394 Potent glucokinase activator; orally bioavailable 10 mg
50 mg
195
775
6114 PF 06409577 Potent and selective allosteric activator of AMPK 10 mg
50 mg
165
635
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 5
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
Inhibitors 5955 eCF 309 Potent mTOR inhibitor 10 mg
50 mg
175
665
6029 FRAX 597 Potent group I PAK inhibitor 10 mg
50 mg
210
820
5632 AZ Dyrk1B 33 Potent and selective Dyrk1B kinase inhibitor 10 mg 260
5742 AZ PFKFB3 67 Potent and selective PFKFB3 inhibitor 10 mg
50 mg
140
505
6071 CZC 25146 Potent LRRK2 inhibitor 10 mg
50 mg
210
820
5834 LTURM 34 Potent DNA-PK inhibitor 10 mg
50 mg
195
760
5756 MLi-2 Potent and selective LRRK2 inhibitor 10 mg
50 mg
255
995
6005 PF 3758309 Potent PAK4 inhibitor; orally available 10 mg
50 mg
115
430
4546 rac-CCT 250863 Potent Nek2 inhibitor 5 mg 290
6015 RAF 265 Raf kinase and VEGFR-2 inhibitor 10 mg
50 mg
215
865
5909 RMM 46 MSK/RSK family kinase inhibitor 10 mg
50 mg
180
720
5968 Ro 3280 Potent and selective PLK1 inhibitor 10 mg
50 mg
225
900
5570 STOCK2S 26016 Lysine deficient protein kinase (WNK) signaling inhibitor 10 mg
50 mg
160
630
Lipases
Inhibitors 5851 JZP 361 Potent and selective reversible MAGL inhibitor 10 mg
50 mg
160
590
6020 URB 602 Non-competitive MAGL inhibitor 10 mg
50 mg
130
470
Category Cat. No. Product Name Description Unit Size Euro
New Products by Pharmacology
6 |
Enzymes – continued
Enzymes
N
N
N
O
N
O
N
O N
NCT 501 (5934)Potent and selective ALDH1A1 inhibitor
N
N
O
O
SNH
OO
N
S
N N
PDD 00017273 (5952)Potent and selective poly (ADP ribose)
glycohydrolase (PARG) inhibitor
N
NH
O
HN
O
N
NOHO
AM 2394 (6034)Potent glucokinase activator;
orally bioavailable
N
N
N NO
O
H2NN
O
H2N
eCF 309 (5955)Potent mTOR inhibitor
NNH
O
N
NH
N
HN
S
N
N
PF 3758309 (6005)Potent PAK4 inhibitor; orally available
O
O
O
HN
S
N
NH2O
PF 06281355 (6004)Selective myeloperoxidase (MPO)
inhibitor; orally bioavailable
O
N
SS
S
O2N
O
CCF 642 (6063)Protein disulfide isomerase (PDI) inhibitor
OH
O
N
O
OH
O
BAY 58-2667 (6052)Potent soluble guanylyl cyclase activator
HN
N
N
N
N
N O
ClS
N
FRAX 597 (6029)Potent group I PAK inhibitor
N
O N
O
HN N
N
O
PF 04449613 (5915)Potent PDE9 inhibitor; brain penetrant
Featured Enzyme Products (continued)
Lyases
Inhibitors 6101 SHIP 2a Cystathione γ lyase (CSE) inhibitor 10 mg
50 mg
140
520
Oxygenases
Inhibitors 6004 PF 06281355 Selective myeloperoxidase (MPO) inhibitor 10 mg
50 mg
160
630
Phosphatases
Inhibitors 5724 NQ 301 Selective CD45 inhibitor 10 mg
50 mg
130
485
Phosphodiesterases
Inhibitors 5695 Eggmanone Potent and selective PDE4 inhibitor; suppresses hedgehog signaling
10 mg
50 mg
160
630
5915 PF 04449613 Potent PDE9 inhibitor; brain penetrant 10 mg 225
Polymerases
Inhibitors 5312 BRACO 19 Telomerase inhibitor 10 mg
50 mg
180
720
Proteases
Inhibitors 6033 (R)-MG 132 Potent 20S proteasome inhibitor 10 mg 270
6019 Diprotin A Dipeptidyl peptidase IV (DPP-IV) inhibitor 10 mg 195
6088 SB 3CT Selective high affinity MMP2 inhibitor 10 mg 275
Reductases
Inhibitors 6063 CCF 642 Protein disulfide isomerase (PDI) inhibitor 10 mg
50 mg
140
505
Synthases/Synthetases
Inhibitors 5791 Bz 423 ATP synthase inhibitor; proapoptotic 10 mg
50 mg
155
590
6111 Zoledronic Acid Potent farnesyl diphosphate (FPP) synthase inhibitor 10 mg
50 mg
80
290
Transferases
Inhibitors 5762 BMS 795311 Potent cholesteryl ester transfer protein (CETP) inhibitor 10 mg 335
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 7
O
O
N
N
N
N
NH2
CP 673451 (5993)Potent and selective PDGFR inhibitor
Enzyme-Linked Receptors
N
N NH2N
O
OH
N
HNO
N Cl
PF 06273340 (6115)Potent and selective pan-Trk inhibitor;
peripherally restricted
Featured Enzyme-Linked Receptor Products
Enzyme-Linked ReceptorsEnzyme-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.
Licensing at TocrisTocris Bioscience has a long tradition of working with scientists to 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 ExpertiseOur 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 UsTo discuss licensing opportunities, please contact our licensing team at [email protected]
Integrins
Inhibitors 6058 ATN 161 α5β1 integrin receptor antagonist 10 mg 210
MET Receptors
Inhibitors 6056 GSK 1363089 Potent inhibitor of MET, VEGFR2, Ron and AXL 10 mg
50 mg
175
665
Receptor Tyrosine Kinases (RTKs)
Inhibitors 5993 CP 673451 Potent and selective PDGFR inhibitor 10 mg 225
6115 PF 06273340 Potent and selective pan-Trk inhibitor; peripherally restricted 10 mg 175
Toll-like Receptors
Agonists 6011 FSL 1 TLR2/6 agonist (also a putative TLR10 ligand) 100 µg 165
Category Cat. No. Product Name Description Unit Size Euro
New Products by Pharmacology
8 |
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.
Ion Channels
NO2
O
O
O
O
O
O
OO
P
P
O
OO
OO
OO
PO
O
O
OO
O
O O
OO
OO
O
O
ci-IP3/PM (6210)Caged inositol triphosphate
O
NH
NO2
HO O
MONNA (5770)Potent TMEM16A (Anoctamin-1) blocker
Cl
NH2
O
(R)-Norketamine (5996)NMDA receptor modulator
Cl
NH2
O
(S)-Norketamine (6112)NMDA receptor modulator
Cl
NH2O
HO
2R,6R-Hydroxynorketamine (6094)Enhances AMPA currents; decreases D-serine
(a NMDA co-agonist); lacks ketamine-related side effects
Cl
NH2O
.HCl
HO
2S,6S-Hydroxynorketamine (6095)Decreases D-serine (a NMDA co-agonist);
antidepressant
N
OHO
O
N
F
PF 05105679 (6003)Selective TRPM8 blocker; orally bioavailable
Featured Ion Channels Products
Calcium Channels
Other 6210 ci-IP3/PM Caged inositol triphosphate 10 µg 200
Chloride Channels
Blockers 6076 Ani 9 Potent and selective TMEM16A (Anoctamin-1; ANO1) blocker 10 mg
50 mg
175
665
5770 MONNA Potent TMEM16A (Anoctamin-1) blocker 10 mg
50 mg
145
560
Glutamate (Ionotropic) Receptors
Other 5996 (R)-Norketamine NMDA receptor modulator; analgesic 10 mg 255
6112 (S)-Norketamine NMDA receptor modulator; analgesic 10 mg 255
6094 2R,6R-Hydroxynorketamine Enhances AMPA currents; decreases d-serine (a NMDA co-agonist); lacks ketamine-related side effects
10 mg 270
6095 2S,6S-Hydroxynorketamine Decreases d-serine (a NMDA co-agonist); antidepressant 10 mg 270
Potassium Channels
Activators 6233 Retigabine KV7 channel activator 10 mg
50 mg
95
325
Blockers 6086 AMP PNP Kir6 (KATP) channel blocker; non-hydrolyzable AMP analog 10 mg 145
Sodium Channels
Blockers 6159 4,9-Anhydrotetrodotoxin Potent and selective NaV1.6 channel blocker 100 µg 200
Transient Receptor Potential Channels
Antagonists 5995 AMG 517 Potent TRPV1 antagonist 10 mg
50 mg
175
680
Blockers 6003 PF 05105679 Selective TRPM8 blocker 10 mg 155
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 9
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.
TransportersTransporters 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.
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 (EC50 = 0.69 μM). ITH 12575 also protects against glutamate-induced excitotoxicity in rat hippocampal slices and oligomycin A/rotenone-induced oxidative stress in neuroblastoma cells in vitro.
Transporters
ITH 12575 (5692)
NH
S
O
Cl
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 protectsagainst glutamate-induced excitotoxitiy in rat hippocampal slices and oligomycin A/rotenone-inducedoxidative stress in neuroblastoma cells in vitro.
LXR-Like Receptors
Agonists 6138 SR 9234 LXR inverse agonist 10 mg
50 mg
160
600
Retinoic Acid Receptors
Antagonists 5758 AGN 193109 Potent retinoic acid receptor (RAR) antagonist 10 mg 270
Na+/Ca2+ Exchanger
Inhibitors 5692 ITH 12575 Mitochondrial Na+/Ca2+ exchange (mNCX) inhibitor. 10 mg
50 mg
195
760
Neurotransmitter Transporters
Inhibitors 6131 (R)-Modafinil Dopamine uptake inhibitor 10 mg
50 mg
100
370
4447 Org 24598 Inhibitor of GlyT1; derivative of Org 24598 lithium salt (Cat. No. 4035).
10 mg
50 mg
190
740
Category Cat. No. Product Name Description Unit Size Euro
Category Cat. No. Product Name Description Unit Size Euro
New Products for Cell Biology
10 |
Potent ULK inhibitor
MRT 68921 Cat. No. 5780
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
N
HN
N
HN
HN
O
N
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
ApoptosisApoptosis 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.
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.
Apoptosis Inducers
Other 5804 Chaetoglobosin A Selectively induces apoptosis of CLL cells; antibiotic 1 mg 195
Autophagy
Inhibitors 5780 MRT 68921 Potent ULK inhibitor; inhibits autophagy 10 mg
50 mg
180
720
DNA, RNA and Protein Synthesis
Inhibitors 5962 3-AP Ribonucleotide reductase inhibitor; also an iron chelator 10 mg
50 mg
115
430
6070 Pladienolide B mRNA splicing inhibitor; antitumor 500 µg 325
5419 PCNA I1 Proliferating cell nuclear antigen (PCNA) inhibitor 10 mg
50 mg
145
560
Lipid Metabolism
Inhibitors 5850 HM 50316 High affinity FABP4 inhibitor 10 mg
50 mg
195
775
Neuronal Metabolism
Other 6250 Filipin III Polyene antibiotic; inhibits formation of pathological isoform of prion protein
1 mg 180
Category Cat. No. Product Name Description Unit Size Euro
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 11
EpigeneticsEpigenetics 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.
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• Selectively induces degradation of BRD4 by the
proteasome• Catalytic mode of action• Negative control, cis MZ 1 (#6155), also available• Licensed from Alessio Ciulli at the University of
Dundee (UK)
UbPROTAC
Target Protein
NH2 NH2
NH2
Ub
E3 ligaseE3 ligase
E2 E2
Ternarycomplex
PolyubiquitinationProteasomePeptide fragments
UbUb Ub
Ub
Catalytic – PROTAC is recycled
How PROTACs Work: Schematic showing PROTACs catalytic mode of action. PROTACs allow the formation of a ternary complex between E3 ubiquitin ligase and a target protein which results in polyubiquitination of the target protein, its recognition by the proteasome and subsequent degradation. PROTACs act catalytically by repeatedly engaging and directing the ubiquitination of target molecules. (Adapted from Timworth et al. (2016) Med.Chem.Comm. 7 2206)
Bromodomains
Inhibitors 5970 BAY 299 Potent and selective BRD1 and TAF1 inhibitor 10 mg
50 mg
145
545
6000 TP 472 Potent BRD9/7 inhibitor 10 mg 190
Other 5999 TP 472N Negative control for TP 472 (Cat. No. 6000) 10 mg 190
Histone Deacetylases
Inhibitors 6010 BRD 4354 HDAC5 and HDAC9 inhibitor 10 mg
50 mg
165
635
6124 (R)-2-Hydroxyglutaric acid disodium salt
KDM4A inhibitor; oncometabolite produced by mutant IDH1 and 2; also NF-κB activator
50 mg 110
Lysine Methyltransferase
Inhibitors 6169 PF 06726304 Highly potent and SAM-competitive EZH2 inhibitor 10 mg 165
PROTACs
Other 6154 MZ 1 (+)-JQ1 based PROTAC that selectively degrades BRD4 in cells 5 mg 325
6155 cis MZ 1 Negative control for MZ 1 (Cat. No. 6154) 5 mg 325
Protein Arginine Methyltransferases
Inhibitors 6008 TP 064 Potent and selective PRMT4 inhibitor 10 mg
50 mg
140
530
5777 GSK 591 Potent and selective PRMT5 inhibitor 10 mg 275
Category Cat. No. Product Name Description Unit Size Euro
New Products for Cell Biology
12 |
Fluorescent ImagingFluorescent 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.
Fluorescent Imaging
O N+N
CO2-
O
O
N
O
O
Janelia FluorTM 549, SE (6147)Fluorescent dye; supplied as an NHS ester for couplingto primary amine groups; compatible with self-labeling
tag systems
Si N+N
CO2-
O
O
N
O
O
Janelia FluorTM 646, SE (6148)Fluorescent dye; supplied as an NHS ester for couplingto primary amine groups; compatible with self-labeling
tag systems
OH2N O
NH2
FFN 200 (5911)Selective fluorescent VMAT2 substrate
Cl NHO
HN
O
N+N
Et
SO3H-O3S
NH
O
NHO
Cl
Cl
IHR-Cy3 (5561)Potent fluorescent Smo antagonist
Featured Fluorescent Imaging Products
Fluorescent Imaging
Other 6065 2-NBDG Fluorescent glucose uptake indicator 5 mg 245
5436 Cyanine 5, SE Red fluorescent dye for the labeling of amines 10 mg 175
5824 Hoechst 33258 Fluorescent dye for labeling DNA 50 mg 65
6147 Janelia Fluor™ 549, SE Cell permeable fluorescent dye; supplied as NHS ester 5 mg 320
6148 Janelia Fluor™ 646, SE Cell permeable fluorescent dye; supplied as NHS ester 5 mg 320
5911 FFN 200 Fluorescent VMAT2 substrate 10 mg 240
5561 IHR-Cy3 Potent fluorescent Smo antagonist 1 mg 180
6046 Naloxone fluorescein acetate Fluorescent opioid antagonist; fluorescent-derivative of naloxone (Cat. No. 0599)
100 µg 175
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 13
Signal TransductionSignal 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.
Signal Transduction
N
N
MeO
MeO
S CN
O SO
O
GSK 319347A (5672)Potent and selective IKKε inhibitor
O
NH2N
NN
NH
Cl
F
Cl
(S)-Crizotinib (6025)Potent MTH1 inhibitor
N
N N
NO
S
HN
EtOO
O
NO
N
N
AX 15836 (5843)Potent and selective ERK5 inhibitor
O
N
NH2
N
HN
O
O
HCl
AMBMP (6043)Wnt canonical signaling activator;
also inhibits tubulin polymerization.
Featured Signal Transduction Products
Cytokine and NF-κB Signaling
Inhibitors 5846 IT 901 NF-κB c-Rel subunit inhibitor 10 mg
50 mg
190
740
4238 PF 184 Potent and selective IKKβ inhibitor 10 mg 270
5300 BI 605906 Selective IKKβ inhibitor 10 mg 270
6107 CP 424174 Inhibitor of IL-1β post-translational processing; indirectly inhibits NLRP3
10 mg
50 mg
140
505
5672 GSK 319347A Potent and selective IKKε inhibitor 10 mg 370
G Proteins (small)
Inhibitors 6025 (S)-Crizotinib MTH1 inhibitor 10 mg
50 mg
155
590
Hedgehog Signaling
Activators 5282 SAG 21k Hedgehog signaling activator; brain penetrant and orally bioavailable
10 mg 255
MAPK Signaling
Inhibitors 5843 AX 15836 Potent and selective ERK5 inhibitor 10 mg 285
6014 Org 48762-0 Selective p38α/β inhibitor; orally bioavailable 10 mg
50 mg
180
705
NO Donors/Precursors
Other 6077 DETA NONOate Nitric oxide donor 10 mg 50
PI 3-K/Akt Signaling
Inhibitors 5835 LTURM 36 PI 3-kinase δ inhibitor 10 mg
50 mg
195
760
6087 Perifosine PKB/Akt inhibitor; also modulates KV2.1 current 10 mg
50 mg
100
370
5919 PI 3065 Potent and selective PI 3-kinase p110δ inhibitor 10 mg
50 mg
215
865
Category Cat. No. Product Name Description Unit Size Euro
New Products for Cell Biology
14 |
ReagentsOur wide and expanding range of research reagents includes biochemicals, buffers, solvents, labels and stains, as well as stable isotopically labeled compounds.
Chemical dimerizer; cell permeable
HaXS8 Cat. No. 4991
NN
N
HN
NH2
O
NH
O O O
F F
F FO
OO
O
Cl
Reagents
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, andSNAP-tag is a trademark of New England BioLabs, Inc.)
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.)
Signal transduction – continued
Transcription Factors
Other 5761 RG 102240 Gene switch ligand for use in inducible gene expression systems 10 mg
50 mg
145
560
Translocation, Exocytosis & Endocytosis
Other 5978 WL 47 - dimer High affinity caveolin-1 ligand 1 mg 145
Wnt Signaling
Activators 6043 AMBMP Wnt canonical signaling activator; also tubulin polymerization inhibitor
10 mg
50 mg
145
560
Inhibitors 5813 NSC 668036 Wnt signaling inhibitor; binds the PDZ domain of the Dishevelled (Dvl) protein
10 mg
50 mg
155
590
Reagents
Other 6117 CORM 2 Carbon monoxide-releasing molecule 100 mg 55
5407 GA3-AM Chemical dimerizer; cell permeable 10 mg
50 mg
80
275
4991 HaXS8 Chemical dimerizer 2 mg 270
6146 LAP Photocrosslinker for hydrogels 500 mg 130
Signal transduction – continued
Category Cat. No. Product Name Description Unit Size Euro
Category Cat. No. Product Name Description Unit Size Euro
NEW PRODUCTS – SPRING AND SUMMER 2017
tocris.com | 15
Scientific ReviewsProduct Guides & Listings Life Science Posters
• GPCRs• Kinases • Cancer Research• Neurodegeneration
• Vascular Reactivity• Gut Hormones • Cancer Metabolism• Addiction
• Ras Oncoproteins• Nicotinic ACh Receptors• Dopamine Receptors• Stem Cells
Life Science Literature from TocrisTocris also provides a wide range of scientific literature free of charge, including the following titles:
To download or request copies, please visit www.tocris.com/requestliterature
Stem Cells
N
HN
N N
N
N
LDN 193189 (6053)Promotes neural induction
of hPSCs; potent and selective ALK2 and ALK3 inhibitor
N
O
NN
NN
Lin28 1632 (6068)Induces differentiation of murine ESCs and
inhibits stemness; RNA binding protein Lin28inhibitor; also bromodomain inhibitor
Featured Stem Cells Products
Stem CellsStem 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.
Reprogramming
Other 6044 AS 8351 Induces reprogramming of fibroblasts into functional cardiomyocytes
10 mg
50 mg
100
370
6066 OAC-2 Oct4 activator; enhances iPSC reprogramming efficiency 10 mg
50 mg
110
390
Stem Cell Differentiation
Other 6053 LDN 193189 Potent and selective ALK2 and ALK3 inhibitor; promotes neural induction of hPSCs
10 mg
50 mg
195
760
6068 Lin28 1632 RNA binding protein Lin28 inhibitor; promotes mESC differentiation; also bromodomain inhibitor
10 mg
50 mg
160
600
Stem Cell Proliferation
Other 5779 NSC 23005 sodium Potently promotes HSC expansion; p18INK inhibitor 10 mg
50 mg
145
560
Category Cat. No. Product Name Description Unit Size Euro
Global [email protected] bio-techne.com/find-us/distributors TEL +1 612 379 2956North America TEL 800 343 7475 Europe | Middle East | Africa TEL +44 (0)1235 529449China [email protected] TEL +86 (21) 52380373
bio-techne.com
For research use or manufacturing purposes only. Trademarks and registered trademarks are the property of their respective owners. BR_NPG_SS2017 15794