Novel 3-Azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity

J Med Chem. 2012 Nov 26;55(22):9531-40. doi: 10.1021/jm301217c. Epub 2012 Nov 2.

Abstract

Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Chick Embryo
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Growth Inhibitors / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Maleimides / chemistry*
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Growth Inhibitors
  • Maleimides
  • Protein Kinase Inhibitors
  • maleimide
  • FLT3 protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3
  • fms-Like Tyrosine Kinase 3
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3