Dipartimento Farmaco Chimico Tecnologico, University of Siena,Via Alcide de Gasperi 2, I-53100 Siena, Italy.
Bioorg Med Chem Lett. 2012 Sep 1;22(17):5579-83. doi: 10.1016/j.bmcl.2012.07.014. Epub 2012 Jul 13.
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.
本文报道了一种用于快速鉴定具有体内疗效的新型抗血管生成药物的靶向/表型联合方法。鉴于酪氨酸激酶 c-Src 在肿瘤血管生成调控中的重要作用，我们对 c-Src 抑制剂的内部文库进行了一系列筛选：在 VEGFR2 上进行计算机筛选、在 HUVEC 细胞上进行体外筛选、ADME 分析、配方筛选，并在斑马鱼模型上进行体内测试。因此，我们鉴定出了一种有前途的低微摩尔浓度即可干扰斑马鱼模型血管生长的抗血管生成候选药物。
