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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).
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
IC50 = 1.8 μM. Exhibits five-fold selectivity for PRMT1 over PRMT6 and >250-fold selectivity over PRMT3 and CARM1.
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.
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.
Reduces Aβ42 levels in vitro (EC50 = 390 nM) and in vivo. Orally bioavailable.
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.
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.
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.
IC50 = 397 nM. Also inhibits STAT3 and STAT5 phosphorylation. Inhibits cell growth and induces apoptosis in cells expressing the JAK2V617F mutation.
Rescues motor neurons undergoing apoptosis (EC50 = 20 nM). Blocks Aβ-induced cortical neuron apoptosis (EC50 ~51 nM). Does not inhibit ERK1 activity. Neuroprotective.
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.
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.
pKd = 8.24. Exhibits no effect on acetylcholine, substance P or serotonin stimulated intestinal contraction.
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.
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.
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).
Kb values are 41 and 560 nM for OX1 and OX2 receptors respectively. Elicits anxiolytic effects in vivo. Brain penetrant and orally available.
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.
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.
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.
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).
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).
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.
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.
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.
IC50 = 25 nM. Displays selectivity for S1P4 against S1P1, S1P2, S1P3 and S1P5 receptors.
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.
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.