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. © 2012 Elsevier Ltd. All rights reserved.
A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation / Radi M.; Evensen L.; Dreassi E.; Zamperini C.; Caporicci M.; Falchi F.; Musumeci F.; Schenone S.; Lorens J.B.; Botta M.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - ELETTRONICO. - 22:17(2012), pp. 5579-5583. [10.1016/j.bmcl.2012.07.014]
A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation
Falchi F.;
2012
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. © 2012 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
