Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr

Bioorg Med Chem Lett. 2007 Nov 1;17(21):6003-8. doi: 10.1016/j.bmcl.2007.07.077. Epub 2007 Aug 22.

Abstract

Inhibition of tumor-induced angiogenesis is a promising strategy in anticancer research. Neovascularization is a process required for both tumor growth and metastasis. Enhanced understanding of the underlying molecular mechanisms has led to the discovery of a variety of pharmaceutically attractive targets. Decades of investigation suggest that vascular endothelial growth factor (VEGF) and its receptors, in particular VEGFR2 or kinase insert-domain-containing receptor (Kdr), play a critical role in the growth and survival of endothelial cells in newly forming vasculature. The clinical utility of inhibitors of this receptor tyrosine kinase is currently under intense investigation. Herein we report our efforts in this arena.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Niacinamide / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • Niacinamide
  • Vascular Endothelial Growth Factor Receptor-2