title: A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: from in silico screening to cyclodextrin formulation.
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.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, University of Siena,Via Alcide de Gasperi 2, I-53100 Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Radi
authors.forename: Lasse
authors.initials: L
authors.lastname: Evensen
authors.forename: Elena
authors.initials: E
authors.lastname: Dreassi
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.forename: Marialessandra
authors.initials: M
authors.lastname: Caporicci
authors.forename: Federico
authors.initials: F
authors.lastname: Falchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Musumeci
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: James B
authors.initials: JB
authors.lastname: Lorens
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000098:blood supply* / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
chemical_list: D020533:Angiogenesis Inhibitors; D003505:Cyclodextrins; D004337:Drug Carriers; D040301:Vascular Endothelial Growth Factor Receptor-2; D016392:Proto-Oncogene Proteins pp60(c-src)