A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation
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- 作者：Marco Radi ; Lasse Evensen ; Elena Dreassi ; Claudio Zamperini ; Marialess ; ra Caporicci ; Federico Falchi ; Francesca Musumeci ; Silvia Schenone ; James B. Lorens ; Maurizio Botta
- 关键词：Angiogenesis ; Kinase ; Zebrafish ; ADME
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：1 September, 2012
- 年：2012
- 卷：22
- 期：17
- 页码：5579-5583
- 全文大小：1000 K
文摘
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.