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Displays 22-fold greater potency towards CK1ε than CK1δ (IC50 values are 32 and 711 nM for CK1ε and CK1δ respectively). ATP competitive. Displays minimal effect on the circadian clock.
Inhibitor of ubiquitin-specific protease (USP) 7 activity (IC50 = 424 nM). Displays uncompetitive inhibition. Also inhibits USP7-mediated p53 deubiquitination (IC50 = 0.8 μM). Stabilizes p53 and inhibits cancer cell growth; induces p53-dependent apoptosis in p53 wild type and null isogenic cancer cell lines.
EC50 = 9 pM. Induces internalization and polyubiquitination of S1P1 in vitro. Selective for S1P1 over S1P2 - S1P4.
Activator of small-conductance Ca2+-activated K+ channels (SK, KCa2); selective for SK1 (EC50 = 8.2 μM in HEK293 cells expressing hSK1) with the profile hSK1 > hSK2 = hSK3 > hIK.
IC50 values are 200 pM, 875 nM and 66 μM for PLK1, PLK3 and PLK2 respectively. Targets the inactive conformation of PLK1. Displays no effect on Aurora kinase A activity. Binds and stabilizes the inactive form of PLK1. Delays cell cycle progression, reduces cell proliferation and induces apoptosis in a range of human cancer cell lines.
EC50 = 0.69 μM. 20-fold selective for KCNQ2/Q3 over KCNQ3/Q5 with no measurable activity over a panel of cardiac ion channels (IC50 > 30 μM for hERG, NaV1.5, L-type channels and KCNQ1). Orally active in several animal models of epilepsy.
Inhibitor of the serine hydrolase enzyme KIAA1363 (AADACL1) (IC50 = 20 nM in mouse brain). Impairs migration, invasion, survival and tumor growth of prostate cancer cell lines in vivo. Reduces monoalkylglycerol ether (MAGE) levels.
Ki values are 4 and 11 nM for 5-HT2A and dopamine D2 receptors respectively. Also displays affinity for a range of other receptors including D1 and D4, 5-HT2C, α1, H1 and M1-4 receptors (Ki values range between 1.9 and 31 nM) . Atypical antipsychotic. Displays anticholinergic properties.
IC50 values are 0.2, 0.1 to 0.3, and 1.2 nM for VEGFR-2, VEGFR-3 and VEGFR-1 respectively. Inhibits angiogenesis and vascular permeability. Displays little activity at 'off-target' protein kinases and exhibits no significant activity in a broad protein kinase screen. Orally available.
Neurotensin antagonist; selective for NTS1 over NTS2 (apparent affinity, Ke, is 36 nM for NTS1). Competitively inhibits binding of [125I]-neurotensin to HT29 and N1E115 cell membranes (IC50 values are 15.3 and 20.4 nM respectively). Orally bioavailable.
IC50 = 11 nM in recombinant human NaV1.8 channels. Reduces tactile allodynia in neuropathic rat models. 3- and 28-fold more potent at NaV1.8 channels compared to NaV1.2 and NaV1.7 channels respectively.
Dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor (IC50 values are 2 and 11 nM respectively). Promotes osteoblast recruitment and activity, and stimulates bone formation in ovariectomized rats.
IC50 = 126 nM. Displays anti-HIV activity in assays using NL4-3 and IIIB strains (EC50 = 21 nM for both strains).
Inhibitor of O6-methylguanine-DNA methyltransferase (MGMT); (IC50 = 0.009 μM in cell-free extracts from HeLa S3 cells); attenuates MGMT activity in vitro and in vivo. Enhances the antitumor activity of temozolomide (Cat. No. 2706) in both human melanoma and MCF-7 xenografts.
Kd = 0.3 nM. Selective for B-Raf against 46 other kinases (Ki app values are 0.16 and 1.72 nM for B-Raf and c-Raf respectively). Decreases anchorage-independent growth of melanoma cell lines. Inhibits ERK phosphorylation and proliferation in tumor cells expressing B-RafV600E.
Neutral antagonist (Ki = 2.5 nM). Displays no significant effect on nuclear receptor corepressor (NCoR) binding; moderately decreases SMRT binding to RAR. Antagonizes agonist-induced coactivator (CoA) recruitment.
Ki values are 190 and 16000 nM for rat α7 and α4β2 receptors respectively. CNS penetrant after systemic administration.
IC50 values are 1.6 and 4 nM for recombinant human ROCK1 and ROCK2 respectively. Displays greater than 30-fold selectivity for ROCK against a panel of serine/threonine kinases. Induces vasorelaxation in preconstricted rat aorta (IC50 = 35 nM); lowers blood pressure in a rat model of hypertension.
Potent agonist of GPR17 (EC50 = 36 pM).
Inhibits the MDM2-p53 interaction (IC50 = 0.09 μM) and activates p53. Antiproliferative agent; induces apoptosis in cancer cells.
Inhibits proteolytic cleavage of amyloid precursor protein (APP) over the Notch pathway. Reduces levels of Aβ in the brain (inhibits Aβ40 and Aβ42 in SH-SY5Y neuroblastoma cells with an IC50 of 0.65 nM); attenuates plaque deposition. Orally bioavailable.
IC50 = 20 nM; displays 75-fold selectivity against PLD1 (IC50 = 1500 nM).
IC50 = 6.3 nM. Exhibits little to no nonspecific target effects against a panel of 229 protein kinases; displays similar target selectivity to KU 55933 (Cat. No. 3544). Inhibits migration and invasion of human glioma cells in vitro.
IC50 = 9.3 nM. Displays antiobesity and antidepressant-like effects in rats and mice. Orally active.
EC50 = 125 nM. Thought to activate the TGF-β signaling pathway; induces Smad2 phosphorylation and increases levels of Nodal expression.
High affinity; Ki = 6-7 nM against wild type c-Met. Displays >1000-fold selectivity for c-Met over a panel of 208 kinases.
IC50 = 2.1 nM. Displays 800-fold cellular selectivity for mTOR over PI3K (cellular EC50 values are 0.25 and 200 nM for mTOR and PI3K respectively). Orally available.
EC50 = 39 nM in CHO-K1 cells expressing human GPR139. Displays no activity against a range of 90 diverse targets.
Ki = 12 nM; EC50 = 43 nM at RXRα receptors. Displays similar RAR agonist activity to bexarotene; exhibits an apparent RXR binding affinity 75% greater than bexarotene.
ATP-competitive pan-Akt kinase inhibitor (IC50 values are 2, 13 and 9 nM for Akt1, 2 and 3 respectively). Also exhibits some inhibition for AMPK, PKA and PAK and PKC isoforms (IC50 < 100 nM). Displays antiproliferative and apoptotic effects in tumor cell lines.
pKi values are 8.9 and 9.2 in rat and human respectively. Brain penetrant and orally active. Has 3- and 100-fold higher affinity than thioperamide (Cat. No. 0644) for rat and human H3 receptors respectively. Suppresses slow-wave sleep; exhibits wake-promoting effects in rodent arousal models.
Ki = 1.2 nM compared to 101 nM for inhibition of Aurora kinase B. Selective over 60 other kinases (IC50 values > 1000 nM). Exhibits good cell permeability and antitumor activity.
IC50 values are 0.35 and 3.8 μM for PPARγ and PPARα respectively. Prevents atherosclerosis progression in E3L.CETP transgenic mice. Also reduces insulin resistance in obese Zucker rats. Orally active.
Reduces tumor size, vascularity and metastasis, and increases apoptosis in human pancreatic cells grown in nude mice. Also exhibits antiangiogenic activity in vitro and in vivo. Sensitizes tumor cells to the cytotoxic effects of gemcitabine (Cat. No. 3259).
Blocks hydrolysis of the endocannabinoid 2-arachidonyl glycerol (2-AG) in vivo in the mouse brain (IC50 = 8 nM). Potentiates depolarization-induced suppression of excitability in cerebellar Purkinje neurons. Exhibits >300-fold selectivity for MAGL over FAAH in vitro.
Ki = 300 nM in vitro. Suppresses FGF-mediated angiogenesis in vivo and decreases VEGF expression. Enhances the therapeutic efficacy of taxol (Cat. No. 1097) in vivo. Orally active.
IC50 = 37 nM. Displays selectivity over 85 other kinases. Inhibits IL-1β-induced TNF-α in a steroid-insensitive in vitro model of oxidative stress.
KD values are 80, 190, 600 and 890 nM for BMK1, DCAMKL2, PLK4 and TNK1 respectively. Displays selectivity over 402 diverse kinases. Blocks growth factor-induced activation of cellular BMK1 and reduces BMK1 activity in in vitro kinase assays. Also reduces BMK1-dependent transactivating activity of MEF2C. Blocks tumor cell proliferation and tumor-associated angiogenesis.
Non-competitive AMPA and kainate receptor antagonist. Analog of GYKI 52466 (Cat. No. 1454). Prolongs the survival time after MgCl2- induced global cerebral ischemia. Exhibits anticonvulsant activity. Also blocks GluK3 homomeric receptors (IC50 = 63 μM) and GluK2b(R)/GluK3 heteroreceptors (IC50 = 32 μM) at high concentrations.
Allosteric potentiator of α7, α4β2 and α4β4 nAChRs; displays selectivity against α3β4 nAChRs. Thought to potentiate agonist-evoked α7 responses by binding within the nAChR transmembrane region.
Selective and potent COX-2 inhibitor (in vitro IC50 values are 0.005 and 140 μM for human recombinant COX-2 and COX-1 respectively). Displays potent anti-inflammatory activity in vivo.
NMDA receptor antagonist selective for NR1/NR2A over NR1/NR2B-containing receptors (pIC50 values are 6.8 and <4.3 respectively in human recombinant NR1/NR2A and NR1/NR2B FLIPR/Ca2+ assays).
Inhibitor of RNA Helicase A (RHA) binding to the oncogenic transciption factor EWS-FLI1. Inhibits Ewing"s sarcoma family tumor (ESFT) cell growth; induces apoptosis.
IC50 values are 16, 6 and 20 nM respectively. Exhibits antiproliferative activity in human tumor cell lines. Blocks cell cycling at G2-M, S and G1 phases; reduces the proportion of actively cycling cells in vivo.
IC50 = 0.1 μM. Displays 100-fold selectivity over NPY Y1, Y4 and Y5 receptors; also displays selectivity against a panel of 50 receptors, ion channels and transporters. Brain penetrant.
Inhibits MEK activity in mouse colon 26 cells (IC50 = 0.33 nM). Inhibits the growth of melanoma cell lines in vitro and in vivo; induces G1-phase cell cycle arrest and apoptosis in a mouse xenograft model. Also inhibits production of proangiogenic cytokines such as VEGF. Orally active.
Ki = 0.23 μM. Reduces inflammatory pain via a cannabinoid receptor-dependent mechanism. Highly efficacious and selective in vivo. Displays no activity at FAAH-2 (IC50 >10 μM).
Ki values are 0.26 and 19.3 nM in CHO cells expressing the human NK3 and NK2 receptor respectively. Also inhibits senktide (Cat. No. 1068) -induced inositol monophosphate formation and intracellular calcium mobilization (IC50 = 10 nM).
Displays potent anti-HIV-1 activity. Prevents the interaction of HIV-1 gp120 and CCR5 (IC50 = 6.4 nM), inhibiting HIV-1 entry. Also inhibits CCL3 (MIP-1α) binding to CCR5.
IC50 = 10 nM. Also blocks TNFα production in LPS-stimulated HWB in vitro (IC50 = 177 nM). Displays 1000-fold selectivity over closely related kinases, including ERK1, MK2 and JNK1-3.
IC50 = 35 nM. Displays selectivity over 46 other kinases including Cdk1 and aurora kinase B. Interferes with chromosome alignment and overrides spindle assembly checkpoint. Inhibits the recruitment of Mad1, Mad2 and centromere protein E (CENP-E) to kinetochores.
Reversibly inhibits currents through mouse, human and rat TRPV4 orthologs (IC50 values are 17, 48 and 133 nM). Also inhibits the endogenous TRPV4-mediated response to 4α-PDH (IC50 = 22 nM). Selective for TRPV4 over TRPV1, TRPV2, TRPV3 and TRPM8 channels.
EC50 = 0.69 μM. Thiazolidinedione (TZD) derivative and antidiabetic agent; improves insulin sensitivity.
IC50 = 2 nM. Inhibits proliferation in BT474 cells and attenuates MAPK signaling.
Increases channel opening efficiency and enhances NMDA receptor responses.
Ki values are 3.4 and 7.9 nM at rat and human CRF1 respectively. Displays >1000-fold selectivity over CRF2 receptors. Suppresses CRF-induced ACTH release in vitro (IC50 = 241 nM) and is brain penetrant.
IC50 = 0.3 nM. Shifts activation gating positively and decreases current magnitude. Displays 100-fold selectivity over other sodium channel subtypes.
Useful for the treatment of cognitive impairment that is associated with schizophrenia and Alzheimer's disease.