Description
SB-216763 (280744-09-4) is a potent and selective inhibitor of glycogen synthase kinase-1 (GSK-3) IC50=34.3 nM.1 Acts at the ATP-binding domain. Displays protective effects in lung fibrosis mouse model.2 Displays neuroprotective effects on cultured neurons.3 SB-216763 maintains mouse embryonic stem cells in a pluripotent state.4?Cell permeable.
Uses
SB 216763 is a potent and selective cell permeale ATP-competitive inhibitor of GSK3a. It stimulates glycogen synthesis in Chang human liver cells.
Uses
SB-216763 was used to inhibit GSK-3β in human brain microvascular endothelial cell line and colorectal cancer cells.
Definition
ChEBI: 3-(2,4-dichlorophenyl)-4-(1-methyl-3-indolyl)pyrrole-2,5-dione is a member of indoles and a member of maleimides.
Biological Activity
Potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor (K i = 9 nM for GSK-3 α ); competes with ATP. Has minimal activity against 24 other protein kinases (IC 50 > 10 μ M). Stimulates glycogen synthesis, gene transcription and is neuroprotective.
Biochem/physiol Actions
SB-216763 is a small molecule that competes with ATP and potently inhibits the activity α and β isozymes of GSK-3. It acts as neuroprotectant and prevents neuronal cell death induced by PI3-kinase pathway. It also delays preconditioning, reduces infarct size and prevents cardiac ischemia.
References
1) Coghlan et al. (2000), Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription; Chem. Biol., 7 793
2) Gurrieri et al. (2010), 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., 332 785
3) Cross et al. (2001), Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurons from death; J. Neurochem., 77 94
4) Kirby et al. (2012), Glycogen synthase kinase 3 (GSK3) inhibitor , SB-216763, promotes pluripotency in mouse embryonic stem cells; PLoS One, 7 e39329
