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BIO is a cell-permeable bis-indolo (indirubin) compound that acts as a highly potent, selective, reversible, and ATP-competitive inhibitor of GSK-3α/β (IC50 = 5 nM). 1,2 Its specificity has been tested against various cyclin-dependent kinases (Cdks) (IC50s = 83, 300, 320, and 10,000 nM for Cdk5/p25, Cdk2/A, Cdk1/B, and Cdk4/D1, respectively). BIO was also tested for its specificity towards many other commonly studied kinases (IC50 ≥ 10 µM), including MAP kinases, PKA, PKC isoforms, PKG, CK, and IRTK. 1,2 Inhibition of GSK by BIO has been shown to result in the activation of the Wnt signaling pathway and sustained pluripotency in human and mouse embryonic stem cells (ESCs).3 BIO is reported to maintain self-renewal in human and mouse ESCs as well as induce the differentiation of neonatal cardiomyocytes.4
1
Meijer, L., Skaltsounis, A., Magiatis, P., et al. GSK-3-selective inhibitors derived from tyrian purple indirubins. Chem Biol101255-1266(2003).
2
Polychronopoulos, P., Magiatis, P., Skaltsounis, A., et al. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem47935-946(2004).
3
Sato, N., Meijer, L., Skaltsounis, L., et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med10(1)55-63(2004).
4
Tseng, A., Engel, F.B., and Keating, M.T. The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem Biol13957-963(2006).
Room temperature
in continental US; may vary elsewhere
SMILES
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O/N=C1/C(=C2\C(=O)Nc3cc(Br)ccc/23)\Nc2ccccc\12
Background Reading
Meijer, L., Skaltsounis, A., Magiatis, P., et al. GSK-3-selective inhibitors derived from tyrian purple indirubins. Chem Biol101255-1266(2003).
Polychronopoulos, P., Magiatis, P., Skaltsounis, A., et al. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem47935-946(2004).
Tseng, A., Engel, F.B., and Keating, M.T. The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem Biol13957-963(2006).
Sato, N., Meijer, L., Skaltsounis, L., et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med10(1)55-63(2004).