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.
Radi M., Evensen L., Dreassi E., Zamperini C., Caporicci M., Falchi F., et al. (2012). A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 22(17), 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.
