GSK-3 Inhibitor IX (CAS 667463-62-9)

GSK-3 Inhibitor IX (BIO) is a cell-permeable, highly potent, selective, reversible, and ATP-competitive inhibitor of glycogen synthase kinase-3α (GSK-3α) and glycogen synthase kinase-3β (GSK-3β; IC₅₀ = 5 nM). GSK-3 plays important roles in numerous signaling pathways that regulate a variety of cellular processes including cell proliferation, differentiation, apoptosis and embryonic development. GSK-3 Inhibitor IX also inhibits phosphoinositide-dependent kinase 1 (PKB Kinase or PDK1), a master kinase responsible for the activation of AKT/PKB, PKC, p70 S6 kinase (S6K), and serum/glucocorticoid regulated kinase (SGK). Research shows that PKB Kinase inhibition halts endothelial cell migration. This small molecule has been been widely used in embryonic stem cell studies to maintain human embryonic stem cells in their undifferentiated state and to sustain expression of the pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog. GSK-3 Inhibitor IX has been shown to induce the differentiation of neonatal cardiomyocytes and maintain self-renewal in both human and mouse embryonic stem cells through Wnt signaling activation. GSK-3 Inhibitor IX is also an inhibitor of Cdk5 and p35.

References

1. Meijer, Laurent., et al., 2003. GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chemistry & biology. 10(12): 1255-66. PMID: 14700633
2. Polychronopoulos, Panagiotis., et al., 2004. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. Journal of medicinal chemistry. 47(4): 935-46. PMID: 14761195
3. Tseng, Ai-Sun., et al., 2006. The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chemistry & biology. 13(9): 957-63. PMID: 16984885
4. Zahler, Stefan., et al., 2007. Inverse in silico screening for identification of kinase inhibitor targets. Chemistry & biology. 14(11): 1207-14. PMID: 18022559
5. Xu, Chong., et al., 2009. Regulation of protein stability by GSK3 mediated phosphorylation. Cell cycle (Georgetown, Tex.). 8(24): 4032-9. PMID: 19923896
6. Rasola, Andrea., et al., 2010. Signal transduction to the permeability transition pore. FEBS letters. 584(10): 1989-96. PMID: 20153328
7. Spokoini, Rachel., et al., 2010. Glycogen synthase kinase-3 plays a central role in mediating glucocorticoid-induced apoptosis. Molecular endocrinology (Baltimore, Md.). 24(6): 1136-50. PMID: 20371704
8. Fairbairn, E.A. et al. 2012. Aquat. Toxicol. 124-125 : 188-196. PMID: 22975441