GSK-3 inhibitor,ATP-competitive,potent and selective
CAS：280744-09-4
分子式：C19H12Cl2N2O2
分子量：371.22
纯度：98%
存储：Store at -20°C

Background:

SB-216763 is a Potent and selective inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50 of 34.3 nM. It competes with ATP and potently inhibits the activity against both GSK-3α and GSK-3β.

GSK-3, one of several known substrates of PKB, is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues.

SB-216763 treatment can protect neurones of both central and peripheral nervous system from cell death which is mediated by PI3K pathway ex vivo [1]. This component was also shown to maintain the pluripotency of mouse embryonic stem cells (mESCs) without exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs) [2].

The component has also been used extensively in various animal models to study the role of GSK-3. In a bleomycin-induced mice lung fibrosis model, SB-216763 administration protected mice from lung inflammation and the subsequent fibrosis, which was associated with decreased production of inflammatory cytokine by macrophages [3]. Besides, treatment of SB-216763 reduced infarct size and prevented cardiac ischemia in a model of regional myocardial ischemia-reperfusion in rats [4].

参考文献:
1.  Cross DA, Culbert AA, Chalmers KA, Facci L, Skaper SD, Reith AD. Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem 2001,77:94-102.
2.  Kirby LA, Schott JT, Noble BL, Mendez DC, Caseley PS, Peterson SC, et al. Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. PLoS One 2012,7:e39329.
3.  Gurrieri C, Piazza F, Gnoato M, Montini B, Biasutto L, Gattazzo C, et al. 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), a glycogen synthase kinase-3 inhibitor, displays therapeutic properties in a mouse model of pulmonary inflammation and fibrosis. J Pharmacol Exp Ther 2010,332:785-794.
4.  Obame FN, Plin-Mercier C, Assaly R, Zini R, Dubois-Rande JL, Berdeaux A, et al. Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3 beta, SB216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via inhibition of the mitochondrial permeability transition pore. J Pharmacol Exp Ther 2008,326:252-258.