Virtual screening for Raf-1 kinase inhibitors based on pharmacophore model of substituted ureas
(0) A three-dimensional (3D) quantitative pharmacophore model was developed from a training set of structurally diverse substituted ureas against Raf-1 kinase, which was well validated to be highly predictive by two methods, namely, test set prediction and cross-validated method. Then a virtual database searching was performed with the pharmacophore model as a 3D query, and the bioactivities of the retrieved hits were predicted by the pharmacophore. Subsequently, molecular docking was carried out on the selected hits whose estimated IC50 were less than 1 μM Finally, 29 hits, which exhibited good estimated activities, high docking scores, similar binding mode to experimentally proven compounds and favorable drug-like properties, were identified as potential leads against Raf-1 kinase. The study may facilitate the discovery and rational design of novel leads with potent inhibitory activity targeting Raf-1 kinase. Softwares used: Catalyst 4.10, Gold 3.0.1
Hui-fang Li Tao Lu Tian Zhu Yong-jun Jiang Sha-sha Rao Li-ye Hu Bo-tao Xin Ya-dong Chen
Department of Organic Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, P Ningbo Institute of Technology, Zhejiang University, Ningbo 315104, P.R.China Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5
国际会议
武汉
英文
179-206
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）