Related Experiment Video
Updated: Jun 16, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Discovery of potent and bioavailable GSK-3beta inhibitors
Leyi Gong1, Don Hirschfeld, Yun-Chou Tan
1Department of Medicinal Chemistry, Roche Palo Alto, Palo Alto, CA 94304, USA. leyi.gong@roche.com
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.
Related Concept Videos
Dipeptidyl Peptidase 4 Inhibitors
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Pharmacogenomics: Identification of New Drug Targets
PI3K/mTOR/AKT Signaling Pathway
Oral Hypoglycemic Agents: Glinides
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...