SB 216763 is a potent and selective ATP-competitive inhibitor of the serine/threonine protein kinase glycogen synthase kinase-3 (GSK-3) α and β isozymes. Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase that is inhibited by an assortment of extracellular stimuli including insulin, growth factors, cell specification factors, and cell adhesion. SB 216763 displays similar potency for GSK-3β with 96% inhibition at 10 μM while exhibiting minimal activity against 24 other protein kinases (IC50 >10 μM). SB 216763 stimulates glycogen synthesis in Chang human liver cells with an EC50 value of 3.6 µM and induces expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. SB 216763 treatment at 25-50 μM reduces cell viability in a dose-dependent manner, and leads to significant increase in apoptosis by 50% at 72 hours due to the specific down regulation of GSK-3β. Administration of SB 216763 at 20 mg/kg significantly prevents lung inflammation and the subsequent fibrosis in bleomycin (BLM)-induced pulmonary inflammation and fibrosis model in mice by significantly blocking the production of inflammatory cytokines MCP-1 and TNF-α by macrophages.
|Cell lines||BXPC-3 cells and MIA-PaCa2 cells|
|Preparation method||BXPC-3 cells were treated with DMSO or the indicated concentration of GSK-3β inhibitors (AR-A014418 and SB216763) over the indicated time course. Relative cell viability was measured using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. B, MIA-PaCa2 cells and the normal human mammary epithelial cell line HMEC, and embryonic lung fibroblast cell line WI38 were treated with DMSO or the indicated GSK-3β inhibitor (25 μmol/L).|
|Concentrations||1, 10, 25, 50µM|
|Incubation time||24, 48 or 72h|
|Animal models||saline induced pulmonary fibrosis model of C57BL/6N mice (12 weeks old)|
|Formulation||25% dimethyl sulfoxide, 25% polyethylene glycol, and 50% saline|
|Administration||intravenously twice a week until day 28|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 20 mg/mL|
Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.
Kirby LA, et al. PLoS One. 2012;7(6):e39329. PMID: 22745733.
Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription.
Coghlan MP, et al. Chem Biol. 2000 Oct;7(10):793-803. PMID: 11033082.
|Related GSK-3 Products|
IM-12 is a potent and selective GSK-3β inhibitor with IC50 of 53 nM, which also enhances canonical Wnt signalling.
SB415286 is a potent GSK3α inhibitor with IC50/Ki of 78 nM/31 nM with equally effective inhibition of GSK-3β.
TDZD-8 is a non-ATP competitive GSK-3β inhibitor with IC50 of 2 μM; minimal inhibitory effect observed on CDK1, casein kinase II, PKA and PKC.
LY2090314 is a potent GSK-3 inhibitor for GSK-3α/β with IC50 of 1.5 nM/0.9 nM; may improve the efficacy of platinum-based chemotherapy regimens. Phase 1/2.
AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with Ki of 6.9 nM and 31 nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.