Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. doi: 10.1016/j.bmcl.2005.12.092. Epub 2006 Feb 3.

Abstract

RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good pharmacokinetic properties in rodents. In a mouse corneal neovascularization assay, this compound inhibited VEGF-induced angiogenesis. Tested in a H460a xenograft tumor model this agent effected significant tumor growth inhibition at doses as low as 50mg/kg.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / blood supply*
  • Neovascularization, Pathologic*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / physiology
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Pyrimidines
  • RO4396686
  • Receptors, Fibroblast Growth Factor
  • Vascular Endothelial Growth Factor A
  • Receptors, Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor Receptor-2