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ID: ALA1154951
Journal: Bioorg Med Chem Lett
Title: Discovery of potent and bioavailable GSK-3beta inhibitors.
Authors: Gong L, Hirschfeld D, Tan YC, Heather Hogg J, Peltz G, Avnur Z, Dunten P.
Abstract: Here we report on the discovery of a series of maleimides which have high potency and good selectivity for GSK-3beta. The incorporation of polar groups afforded compounds with good bioavailability. The most potent compound 34 has an IC(50) of 0.6nM for GSK-3beta, over 100-fold selectivity against a panel of other kinases, and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3beta protein with 34 bound revealed the binding mode of the template and provided insights for future optimization opportunities.
CiteXplore: 20138512