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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemistry*
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Cyclodextrins / chemistry
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Drug Carriers / chemistry
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Drug Discovery / methods*
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Embryo, Nonmammalian / blood supply*
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Embryo, Nonmammalian / drug effects
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Human Umbilical Vein Endothelial Cells
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Humans
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Models, Animal
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Physiologic / drug effects*
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Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
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Proto-Oncogene Proteins pp60(c-src) / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
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Zebrafish / embryology
Substances
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Angiogenesis Inhibitors
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Cyclodextrins
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Drug Carriers
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Vascular Endothelial Growth Factor Receptor-2
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Proto-Oncogene Proteins pp60(c-src)