2. Academic Validation
  3. Discovery of potent and bioavailable GSK-3beta inhibitors

Discovery of potent and bioavailable GSK-3beta inhibitors

  • Bioorg Med Chem Lett. 2010 Mar 1;20(5):1693-6. doi: 10.1016/j.bmcl.2010.01.038.
Leyi Gong 1,  Don Hirschfeld,  Yun-Chou Tan,  J Heather Hogg,  Gary Peltz,  Zafrira Avnur,  Pete Dunten
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Roche Palo Alto, Palo Alto, CA 94304, USA. [email protected]
PMID: 20138512 DOI: 10.1016/j.bmcl.2010.01.038
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100207
    99.63%, GSK-3β Inhibitor