Steering target selectivity and potency by fragment-based de novo drug design

Angew Chem Int Ed Engl. 2013 Sep 16;52(38):10006-9. doi: 10.1002/anie.201304847. Epub 2013 Aug 26.

Abstract

Kinase inhibitors: Ligand-based de novo design is validated as a viable technology for rapidly generating innovative compounds possessing the desired biochemical profile. The study discloses the discovery of the most selective vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor (right in scheme) known to date as prime lead for antiangiogenic drug development.

Keywords: VEGFR; drug design; drug discovery; fragment-based design; kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design*
  • Drug Discovery
  • Humans
  • Ligands
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry*
  • Vascular Endothelial Growth Factor A / chemistry*

Substances

  • Ligands
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A