GSK 3 Inhibitor IX

GSK 3 Inhibitor IX (6-Bromoindirubin-3'-oxime; BIO) is a potent, selective, reversible and ATP-competitive inhibitor of GSK-3α/β and CDK1-cyclinB complex with IC₅₀s of 5 nM/320 nM/80 nM for (GSK-3α/β)/CDK1/CDK5, respectively. IC50 & Target: IC50: 5 nM (GSK-3α/β), 320 nM (CDK1), 80 nM (CDK5)^[1] In Vitro: GSK 3 Inhibitor IX (BIO) is a specific inhibitor of glycogen synthase kinase-3 (GSK-3), with IC₅₀ of 5 nM for GSK-3α/β, shows > 16-fold selectivity over CDK5. GSK 3 Inhibitor IX interacts within the ATP binding pocket of these kinases, reduces β-catenin phosphorylation on a GSK-3-specific site in cellular models, closely mimicks Wnt signaling in Xenopus embryos^[1]. In human and mouse embryonic stem cells, GSK 3 Inhibitor IX (BIO) maintains the undifferentiated phenotype and sustains expression of the pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog. GSK 3 Inhibitor IX (BIO)-mediated Wnt activation is functionally reversible, as withdrawal of the compound leads to normal multidifferentiation programs in both human and mouse embryonic stem cells^[2]. GSK 3 Inhibitor IX (BIO) promotes proliferation in mammalian cardiomyocytes^[3]. GSK 3 Inhibitor IX (BIO) is also a pan-JAK inhibitor, with IC₅₀ values of 0.03, 1.5, 8.0, 0.5 μM for TYK2, JAK1, JAK2 and JAK3, respectively. GSK 3 Inhibitor IX (BIO) selectively inhibits phosphorylation of STAT3 and induces apoptosis of human melanoma cells^[4]. In Vivo: GSK 3 Inhibitor IX (BIO) (50 mg/kg, p.o.) suppresses melanoma tumor growth in a mouse xenograft model^[4].