1. A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: from in silico screening to cyclodextrin formulation.
- Author
-
Radi M, Evensen L, Dreassi E, Zamperini C, Caporicci M, Falchi F, Musumeci F, Schenone S, Lorens JB, and Botta M
- Subjects
- Animals, Cyclodextrins chemistry, Drug Carriers chemistry, Embryo, Nonmammalian drug effects, Human Umbilical Vein Endothelial Cells, Humans, Models, Animal, 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 chemistry, Angiogenesis Inhibitors pharmacology, Drug Discovery methods, Embryo, Nonmammalian blood supply, Neovascularization, Pathologic drug therapy, Neovascularization, Physiologic drug effects
- Abstract
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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF