An inhibitor of GSK3β signaling
IC50: 390 nM for GSK-3β
GSK-3β Inhibitor II is a GSK-3β inhibitor.
Glycogen Synthase Kinase-3 (GSK-3), a protein-serine kinase, is implicated in the hormonal control of various regulatory proteins. A number of substrates have been identified, which implicates GSK-3 in the regulation of several physiological processes. Moreover, it has been reported that compounds that specifically inhibit GSK-3 activity may be useful in the treatment of diabetes.
In vitro: In a previous study, by using a virtual screening strategy based on a methodology derived from the CATS molecular descriptor, a novel compound class including GSK-3β Inhibitor II with inhibitory activity against the GSK-3 enzyme was identified via scaffold hopping. GSK-3β Inhibitor II was found to be a potent inhibitor of GSK-3β with the IC50 value of 390 nM. However, GSK-3β Inhibitor II was not able to inhibit another GSK-3 isoform, GSK-3α [1]. Another study found that GSK-3β Inhibitor II could block the functional regulation of p53 through inhibiting GSK-3β, decreasing MDM2 levels, and modulating mitochondrial p53 apoptotic signaling [2].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
参考文献:
[1] Naerum, L.?,Nrskov-Lauritsen, L. and Olesen, P.H. Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors. Bioorg.Med.Chem.Lett. 12(11), 1525-1528 (2002).
[2] Watcharasit, P.?,Bijur, G.N.,Song, L., et al. Glycogen synthase kinase-3beta (GSK3beta) binds to and promotes the actions of p53. J.Biol.Chem. 278(49), 49972-48879 (2003).
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