A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: from in silico screening to cyclodextrin formulation

Bioorg Med Chem Lett. 2012 Sep 1;22(17):5579-83. doi: 10.1016/j.bmcl.2012.07.014. Epub 2012 Jul 13.


A combined targeted/phenotypic approach for the rapid identification of novel antiangiogenics with in vivo efficacy is herein reported. Considering the important role played by the tyrosine kinase c-Src in the regulation of tumour angiogenesis, we submitted our in-house library of c-Src inhibitors to a sequential screening approach: in silico screening on VEGFR2, in vitro screening on HUVEC cells, ADME profiling, formulation and in vivo testing on a zebrafish model. A promising antiangiogenic candidate able to interfere with the vascular growth of a zebrafish model at low micromolar concentration was thus identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cyclodextrins / chemistry
  • Drug Carriers / chemistry
  • Drug Discovery / methods*
  • Embryo, Nonmammalian / blood supply*
  • Embryo, Nonmammalian / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Models, Animal
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects*
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Zebrafish / embryology


  • Angiogenesis Inhibitors
  • Cyclodextrins
  • Drug Carriers
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins pp60(c-src)