Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry

Chem Commun (Camb). 2012 Mar 14;48(22):2788-90. doi: 10.1039/c1cc15851a. Epub 2012 Feb 8.

Abstract

Novel bisaryl maleimide derivatives to mimic natural kinase inhibitors were prepared through click chemistry. A highly selective hit was discovered in a 124-kinase-assay, and docking studies revealed a π-π stacking interaction with the Phe67 at the P-loop of GSK-3β kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Click Chemistry*
  • Computer Simulation
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Maleimides / chemistry
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary

Substances

  • Maleimides
  • Protein Kinase Inhibitors
  • maleimide
  • Protein Kinases
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3