Featured New Products 2014

Highlighted products added to the Tocris Bioscience range during 2014

December 2014

TA1 receptor antagonist/inverse agonist
4518 | EPPTB

Exhibits a higher potency at the mouse trace amine 1 (TA1) receptor than the rat and human TA1 receptors (IC50 values are 27.5, 4539 and 7487 nM, respectively). Also displays inverse agonism, reducing basal cAMP levels in vitro (IC50 = 19 nM).

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Selective BAZ2 bromodomain inhibitor
5266 | BAZ2-ICR

Kd values are 109 and 170 nM for BAZ2A and BAZ2B respectively. Exhibits 15-fold selectivity for the BAZ2 bromodomain over the CERC2 bromodomain and >100-fold selectivity over a range of other bromodomains. Accelerates FRAP recovery in a BAZ2A FRAP assay.

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High affinity ghrelin receptor agonist
5272 | MK 0677

pKi = 8.14. Growth hormone (GH) secretagog; stimulates GH release from rat pituitary cells in vitro (EC50 = 1.3 nM) and enhances GH plasma levels in vivo. Also attenuates isoproterenol-induced lipolysis in rat adipocytes in vitro. Orally bioavailable.

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Activator of BKCa (KCa1.1) channels
5276 | NS 19504

EC50 = 11 μM. Activates BK channels in native smooth muscle cells and reduces spontaneous phasic contractions in bladder strips ex vivo. Displays no effect on contractions induced by a high K+ concentration or at 65 other receptors tested including L- and N- type Ca2+ channels, Nav, KATP and hERG channels.

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Potent anaplastic lymphoma kinase inhibitor
5310 | ASP 3026

IC50 = 3.5 nM. Inhibits ALK tyrosine kinase activity in an ATP-competitive manner. Also inhibits ACK and ROS1 activity (IC50 values are 5.8 and 8.9 nM respectively). Decreases cell viability and proliferation, and induces apoptosis of NPM-ALK+ T-cell anaplastic large-cell lymphoma (ALCL) cells in vitro. Orally available.

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November 2014

Potent negative allosteric modulator of LFA-1
4776 | BIRT 377

Kd = 26 nM. Binds to the I-domain of LFA-1. Reversibly inhibits LFA-1 mediated binding of SKW3 leukemia cells to ICAM-1. Inhibits SEB superantigen-induced IL-2 production from lymphocytes in vitro and attenuates the SEB-induced increase in IL-2 plasma levels in a mouse model in vivo. Orally available.

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Neuropilin 1 receptor antagonist
4931 | EG 00229

Inhibits VEGFA binding to the NRP1 b1 domain. Has no effect on VEGFA binding to VEGFR-1 and VEGFR-2. Reduces VEGFA-induced VEGFR-2 tyrosine phosphorylation in HUV-EC-C endothelial cells. Also attenuates VEGFA-induced HUV-EC-C cell migration and reduces A549 lung carcinoma cell viability in vitro. Increases chemosensitivity of A549 cells in combination with Taxol (Cat. No. 1097).

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Nonpeptide p75NTR ligand; neuroprotective
5046 | LM11A 31

Blocks p75-mediated cell death and also increases proliferation and survival of hippocampal neural progenitors. Exhibits no effect on nerve growth factor (NGF) binding to TrkA. Prevents and reverses atrophy of cholinergic neurites, as well as reversing Alzheimer's Disease (AD) pathologies in mid- to late-stage AD mice models. Shown to promote functional recovery in a mouse model of spinal cord injury. Orally available and brain penetrant.

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Potent and selective mGlu7 antagonist
5248 | XAP 044

IC50 = 88 nM; inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice. Displays no activity on the LTP of mGlu7 deficient mice. Exhibits novel activity by binding to the mGlu7 Venus flytrap domain (VFTD). Exhibits anti-anxiety effects in rodent models. Brain penetrant.

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mTOR inhibitor; antitumor
5264 | Temsirolimus

Inhibits tumor growth in breast cancer cell lines (IC50 values are 1.6 and 4.3 nM for SKBr3 and BT474, respectively). Inhibits HIF-1α-mediated VEGF production in breast cancer cell lines (BT474 and MDA-MB-231). Directly inhibits serum and VEGF mediated endothelial cell proliferation and morphogenesis in vitro and vessel formation in vivo. Causes G1/S cell cycle arrest in multiple cancer cell lines. Antiangiogenic.

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October 2014

High affinity and selective EP4 antagonist
3565 | ONO AE3 208

Ki values are 1.3, 30, 790 and 2400 nM for EP4, EP3, FP and TP receptors respectively. Displays no affinity for EP1, EP2, DP or IP receptors (Ki >10 μM). Inhibits PGE2-induced IL-8 production in colonic epithelial caco-2 cells and attenuates PGE2 inhibition of natural killer T cell activation. Suppresses recovery from experimentally-induced colitis. Orally active.

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Potent and selective G9a/GLP histone lysine methyltransferase inhibitor
5163 | A 366

IC50 = 3.3 nM. Exhibits >1000 selectivity for G9a/GLP over 21 other methyltransferases. Decreases levels of lysine 9 dimethylation on histone H3 (H3K9Me2) in PC3 cells.

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Potent and selective lactate dehydrogenase A inhibitor
5189 | GSK 2837808A

IC50 values are 1.9 and 14 nM for LDHA and LDHB respectively. Inhibits lactate production in multiple cancer cell lines. Reduces glucose uptake and enhances mitochondrial oxygen consumption in Snu398 hepatocellular carcinoma cells. Inhibits proliferation and induces apoptosis in Snu398 cells. Cell permeable.

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Potent and selective FABP4 inhibitor
5258 | BMS 309403

Ki values are <2, 250 and 350 nM for FABP4, FABP3 and FABP5 respectively. Decreases fatty acid uptake in adipocytes in vitro and reduces atherosclerotic lesion area in a mouse model of atherosclerosis. Reduces blood glucose levels and increases insulin sensitivity in a mouse model of obesity. Orally active.

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Potent MTH1 inhibitor
5280 | SCH 51344

Kd = 49 nM. Inhibits Ras-induced malignant transformation and increases α-actin promoter-driven CAT activity in Ras-transformed cells. Has no effect on Ras-induced ERK and JNK activation. Inhibits Ras-induced membrane ruffling in REF-52 fibroblasts and blocks anchorage-independent growth of Ras-transformed tumor cell lines. Also induces DNA damage in SW480 colon cancer cells.

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September 2014

DNA methyltransferase inhibitor
5155 | SGI 1027

Inhibits the mammalian DNA methyltransferases DNMT3B, DNMT3A and DNMT1 (IC50 values are 7.5, 8 and 12.5 μM with Poly(dl-dC) as the substrate). Reactivates silenced tumor suppressor genes by reducing CpG island hypermethylation.

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Potent C5a receptor peptide antagonist
5196 | PMX 205

IC50 = 31 nM. Ameliorates experimentally-induced colon inflammation in mice. Reduces fibrillar amyloid deposits, decreases hyperphosphorylated tau levels and rescues cognitive function in a mouse model of Alzheimer's Disease. Orally active and brain penetrant.

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ATP-competitive inhibitor of IGF1R
5247 | NVP ADW 742

IC50 = 0.1-0.2 μM. Also inhibits c-Kit kinase activity (IC50 in the range of 3-5 μM). Exhibits a synergistic effect with imatinib, enhancing the sensitivity of multiple small cell lung cancer cell lines to the chemotherapeutics etoposide (Cat. No. 1226) and carboplatin (Cat. No. 2626).

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Potent and selective FFA4 (GPR120) agonist
5257 | GSK 137647

pEC50 values are 6.3, 6.2 and 6.1 at the human, mouse and rat receptor, respectively. Exhibits ≥100-fold selectivity against a panel of 61 targets including FFA1, FFA2 and FFA3. Enhances glucose-stimulated insulin secretion in MIN6 cells. Induces intracellular calcium accumulation in U2OS cells; this activity is inhibited by AH 7614 (Cat. No. 5256).

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Potent and selective smoothened (Smo) receptor antagonist
5262 | PF 5274857

Ki = 4.6 nM. Exhibits >1000-fold selectivity for Smo over a panel of other receptors, ion channels and enzymes. Inhibits Shh-induced Hedgehog signaling in MEF cells. Induces tumor regression in a medulloblastoma allograft mouse model. Orally available and brain penetrant.

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August 2014

Potent LIM kinase inhibitor; antitumor
4745 | LIMKi 3

IC50 values are 7 and 8 nM for LIMK1 and LIMK2 respectively. Inhibits cofilin phosphorylation in MDA-MB-231 breast cancer cells. Reduces MDA-MB-231 tumor cell invasion in a 3D matrigel invasion assay.

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Potent and selective BRD4 bromodomain inhibitor
5173 | MS 436

Ki = 30 - 50 nM for BrD1; exhibits 10-fold selectivity for BrD1 over BrD2. Blocks BRD4 transcriptional activity in lipopolysaccharide-induced production of both nitric oxide and IL-6 in mouse macrophages (IC50 values are 3.8 and 4.9 μM, respectively).

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sFRP-1 inhibitor; increases Wnt signaling
4767 | WAY 316606

Inhibits secreted frizzled-related protein-1 (sFRP-1) (IC50 = 0.65 μM); prevents sFRP-1 from interacting with Wnt and thus increases Wnt signaling. Increases total bone area in a murine calvarial organ culture assay.

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Potent NPSR antagonist
5161 | ML 154

pA2 = 9.98. Inhibits neuropeptide S-induced ERK phosphorylation over cAMP responses and calcium responses (IC50 values are 9.3, 22.1 and 36.5 nM, respectively). Appears to modulate addictive behavior in vivo. Displays no activity against vasopressin V1B receptors. Brain penetrant.

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Potent kinesin spindle protein inhibitor
5109 | SB 743921

Ki = 0.1 nM. Induces cell mitotic arrest and apoptosis in vitro. Inhibits the growth of a range of tumor cells in vitro, including colon (HCT 116), prostate (PC-3) and leukemia (K-562) cancer cell lines. Causes tumor regression in human tumor xenograft models in vivo, including colon (Colo205), lung (H69) and breast (MCF7) cancer cell xenografts.

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July 2014

Selective MEK5 and ERK5 inhibitor
4842 | BIX 02189

IC50 values are 1.5 and 59 nM respectively. Inhibits sorbitol-induced ERK5 phosphorylation in HeLa cells. Selective for MEK5 and ERK5 over MEK1/2, ERK1/2 and a panel of 87 kinases. Induces apoptosis in acute myeloid leukemia tumor cells.

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Selective DDR1 inhibitor
5077 | DDR1-IN-1

Selective discoidin domain receptor 1 (DDR1) tyrosine kinase inhibitor (IC50 values are 105 and 413 nM for DDR1 and DDR2 respectively). Inhibits integrin-induced DDR1 autophosphorylation in an osteosarcoma cell line.

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Potent and selective PERK inhibitor
5107 | GSK 2606414

IC50 = 0.4 nM. Inhibits thapsigargin-induced PERK phosphorylation in lung carcinoma A549 cells. Attenuates subcutaneous pancreatic human tumor xenograft growth in mice. Orally bioavailable.

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Dimeric Smac mimetic; potent IAP inhibitor
5141 | AZD 5582

IC50 values are 15, 15 and 21 nM for XIAP, cIAP1 and cIAP2 respectively. Binds to the BIR3 domain of XIAP to prevent interaction with caspase-9. Causes degradation of cIAP1 and cIAP2 and induces apoptosis in MDA-MB-231 breast cancer cells. Causes tumor regression in MDA-MB-231 xenograft-bearing mice.

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Potent and selective ATR kinase inhibitor
5198 | AZ 20

IC50 = 5 nM. Exhibits 7.6-fold selectivity over mTOR and selectivity over a panel of 442 kinases, including ATM kinase, PI3-K isoforms, and DNA-PK. Inhibits cell growth in cell lines with high baseline levels of replication stress. Displays antitumor effects in vivo.

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June 2014

Melanocortin MC4 receptor antagonist
4854 | ML 00253764

IC50 values are 0.32, 0.81 and 2.12 μM for MC4, MC3 and MC5 receptors respectively. Decreases cAMP accumulation in HEK-293 cells expressing the MC4 receptor. Increases food intake and reduces loss of lean body mass in tumor bearing mice. Brain penetrant.

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Highly potent, selective inhibitor of integrin α4β1
5051 | BIO 5192

Kd < 10 pM. Selectively binds α4β1 over a range of other integrins (IC50 values are 1.8, 138, 1053, > 500 and > 10,000 nM for α4β1, α9β1, α2β1, α4β7 and α11bβ3, respectively). Induces a 30-fold increase in mobilization of murine hematopoietic stem and progenitor cells.

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High affinity, selective urotensin II (UT) receptor antagonist
5110 | GSK 1562590

pKi values are 9.14, 9.28, 9.34, 9.64 and 9.66 at monkey, human, mouse, cat and rat recombinant receptors respectively. Exhibits selectivity for UT receptors over a range of GPCRs, ion channels, enzymes and neurotransmitter transporters. Orally active.

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Selective PRMT1 arginine methyltransferase inhibitor
5128 | C 21

IC50 = 1.8 μM. Exhibits five-fold selectivity for PRMT1 over PRMT6 and >250-fold selectivity over PRMT3 and CARM1.

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Highly potent Porcn inhibitor
5148 | Wnt-C59

Potently inhibits Porcupine (Porcn), a membrane-bound O-acyltransferase (MBOAT) (IC50 = 74 pM). Shown to inhibit Wnt signaling pathways. Downregulates Wnt/β-catenin target genes. Cell permeable and bioavailable.

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May 2014

Potent and selective mTOR inhibitor
4893 | XL 388

IC50 = 9.9 nM. Inhibits mTOR activity in an ATP-competitive manner. Exhibits >300-fold selectivity for mTOR over PI 3-K and a range of other kinases. Displays antitumor activity in athymic nude mice implanted with tumor xenografts.

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γ-secretase modulator; reduces Aβ42 levels
4898 | TC-E 5006

Reduces Aβ42 levels in vitro (EC50 = 390 nM) and in vivo. Orally bioavailable.

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Potent and selective, competitive motilin receptor antagonist
4934 | MA 2029

IC50 = 4.9 nM. Selective for the motilin receptor over a range of other receptors and ion channels. Inhibits motilin-induced duodenal muscle contractions in vitro. Orally active.

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Potassium channel modulator; exerts subtype-specific effects
4949 | MaxiPost

Acts as a positive modulator at neuronal Kv7 channels and calcium-activated K+ channels (BKCa) in HEK293 cells. Displays negative modulatory activity at Kv7.1 channels (Ki = 3.7 μM) and GABAA receptors. Displays anxiolytic activity in vivo.

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Potent and selective IR and IGF1R inhibitor
5111 | GSK 1838705

IC50 values are 1.6 and 2 nM, respectively. Also inhibits ALK (IC50 = 0.5 nM). Blocks proliferation of cancer cell lines in vitro, retards growth of human tumor xenografts in vivo, and causes complete regression of ALK-dependent tumors in vivo. Displays >800-fold selectivity over a panel of 44 kinases including JNK. Orally bioavailable.

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April 2014

JAK2 inhibitor
4580 | Atiprimod

IC50 = 397 nM. Also inhibits STAT3 and STAT5 phosphorylation. Inhibits cell growth and induces apoptosis in cells expressing the JAK2V617F mutation.

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Inhibitor of JNK signaling
4924 | CEP 1347

Rescues motor neurons undergoing apoptosis (EC50 = 20 nM). Blocks Aβ-induced cortical neuron apoptosis (EC50 ~51 nM). Does not inhibit ERK1 activity. Neuroprotective.

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Potent and selective Ack1 inhibitor
4946 | AIM 100

IC50 = 22 nM. Exhibits selectivity for Ack1 over ABL1, BTK, Lck and LYN; exhibits no inhibition of 25 other kinases. Suppresses phosphorylation of Tyr267 of the androgen receptor in prostate cancer cells.

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SMARCA4 and PB1 inhibitor
5072 | PFI 3

Potent and selective polybromo 1 and SMARCA4 inhibitor (Kd values are 48 and 89 nM respectively). Also inhibits SMARCA2. Displays 30-fold selectivity over other sub-family branches. Accelerates FRAP recovery in cells at a concentration of 1 μM.

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Selective motilin receptor antagonist
5074 | ANQ 11125

pKd = 8.24. Exhibits no effect on acetylcholine, substance P or serotonin stimulated intestinal contraction.

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March 2014

Potent and selective PLK2 inhibitor
4459 | TC-S 7005

Selective for PLK2 over PLK3 and PLK1 (IC50 values are 4, 24 and 214 nM respectively). Induces mitotic arrest and cell death in HCT 116 colorectal cells.

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Potent and selective GPR109A (HCA2) agonist
4622 | MK 1903

Exhibits greater potency than Niacin in a whole cell HTRF-cAMP assay (EC50 values are 12.9 and 51 nM respectively). Exhibits no binding at the GRP109B receptor. Shown to lower plasma free fatty acid levels in humans.

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Potent, selective MAGL inhibitor
4872 | KML 29

Exhibits potent inhibition of human, mouse and rat MAGL (IC50 values are 5.9, 15 and 43 nM, respectively). Exhibits no detectable inhibition of FAAH (IC50 > 50000 nM). Potently and selectively blocks hydrolysis of 2-arachidonoylglycerol (2-AG) in mice (IC50 = 2.5 nM and >50 μM for 2-AG and AEA respectively).

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Potent and selective OX1 antagonist
4983 | ACT 335827

Kb values are 41 and 560 nM for OX1 and OX2 receptors respectively. Elicits anxiolytic effects in vivo. Brain penetrant and orally available.

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Orally active AdipoR1 and AdipoR2 agonist; antidiabetic
5096 | AdipoRon

Kd values are 1.8 and 3.1 μM respectively. Activates AMPK and PPARα signaling; ameliorates insulin resistance, dyslipidemia and glucose intolerance in db/db mice. Orally active antidiabetic agent.

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February 2014

Potent, selective EGFR and ErbB2 inhibitor
5022 | BMS 599626

IC50 values are 22 nM and 32 nM respectively. Also inhibits HER4 (IC50 = 190 nM). Inhibits EGFR and ErbB2 with 100-fold greater potency than MEK and Lck. Antiproliferative agent in vitro and anti-tumorigenic agent in vivo. Orally bioavailable.

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Selective NaV1.3 and NaV1.1 blocker
5066 | ICA 121431

IC50 values are 13 and 23 nM respectively. Exhibits up to 1,000 fold selectivity against other TTX-sensitive or resistant sodium channels. Interacts with an inhibitory interaction site distinct from those bound by TTX and local anesthetic-like modulators.

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Monoacylglycerol (MAGL) inhibitor
4906 | JW 642

Potent and selective monoacylglycerol lipase (MAGL) inhibitor (IC50 = 3.7 nM). Displays >1000-fold selectivity for MAGL over fatty acid amide hydrolase (IC50 = 20.6 μM). Analog of JZL 195 (Cat. No. 4715).

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Potent Smoothened (Smo) receptor antagonist
4917 | M 25

IC50 = 5 nM. Inhibits the Hedgehog signaling pathway. Inhibits Shh induced Gli luciferase reporter activity in Shh-light 2 cells (IC50 = 5 nM). Antagonizes GSA-10 and SAG-mediated differentiation of the C3H10T1/2 cell line (IC50 values are 69 and 115 nM, respectively).

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Potent dual Fms/KIT inhibitor
5102 | PLX 647

Potent dual KIT/Fms inhibitor (IC50 values are 16 and 28 nM respectively). Inhibits BCR-FMS cell proliferation and osteoclast differentiation in vitro (IC50 values are 92 and 170 nM respectively). Attenuates LPS-induced TNFα and IL-6 release, and mast cell activation in vivo.

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January 2014

Inhibitor of Hedgehog (Hh) signaling
4838 | AZ 12080282

IC50 <0.012 μM in a firefly reporter assay against the Hh pathway. Shown to displace cyclopamine in HeLa cells expressing Smoothened. Exhibits selectivity against p38α. Orally bioavailable.

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TrkB receptor antagonist
5062 | Cyclotraxin B

Inhibits BDNF-induced TrkB activity (IC50 = 0.30 nM). Allosterically alters TrkB receptor conformation but does not alter BDNF binding. Prevents BDNF-induced cold allodynia in mice. Also shown to exhibit putative anxiolytic properties in mice.

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Potent and selective S1P4 antagonist
4679 | CYM 50358

IC50 = 25 nM. Displays selectivity for S1P4 against S1P1, S1P2, S1P3 and S1P5 receptors.

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Potent and selective PDE10A inhibitor
4572 | TC-E 5005

IC50 values are 7.28, 239, 779, 919, 3100 and 3700 nM at PDE10A, 2A, 11A, 5A, 7B and 3A respectively and >5000 nM at PDE1B, 4A, 6, 8A and 9A. Reverses MK 801-induced hyperactivity in vivo.

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Potent Lck inhibitor
3567 | TC-S 7003

IC50 values are 0.007, 0.021, 0.042 and 0.20 μM for Lck, Lyn, Src and Syk kinases respectively. Displays >1000-fold selectivity for Lck over MAPK, CDK and RSK family representatives. Inhibits T-cell proliferation in vitro and inhibits arthritis in two in vivo models. Orally active.

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