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GSK-3 inhibitor IX (BIO) is a potent, selective, cell-permeable, ATP-competitive and reversible inhibitor of GSK-3α (glycogen synthase kinase-3α) and GSK-3β (lycogen synthase kinase-3β) (IC50 = 5nM for GSK-3β). [1]

GSK3 (glycogen synthase kinase-3) is a serine/threonine protein kinase which contributes to cell survival, diabetes, insulin resistance and Alzheimer's diseases. It is contributed to β-catenin/Wnt signaling pathway.

BIO facilitated the proliferation in mammalian cardiomyocytes by increasing the proliferation potential of cardiomyocytes. It induced S phase entry and beta-catenin activity in neonatal cardiomyocyte. [3] BIO also activated Wnt signaling and involved in maintaining pluripotency in human and mouse ESCs (embryonic stem cells). [2] In Cos-1 cells treated with 5 μm BIO for 24 hours, phosphorylation of β-catenin was inhibited on GSK-3 specific sites. In cell line deficient for AhR or ARNT, 10 μm BIO treatment for 24 hours showed its effect is through a direct and AhR- independent pathway.[1]

In vivo study showed BIO activated maternal Wnt signaling pathway in Xenopus embryos. It caused a hyper dorso-anteriorization at the expense of trunk and tail in a dose-response manner. It also activated the dorsal genes (siamois and chordin) ectopically. [1]

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