Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors
Pharmacophore models of Polo-like kinase-1 (PLK1) inhibitors have been established by using the Hip Hop and Hypo Cen algorithms implemented in the Catalyst software package. The best quantitative phar macophore model, Hypol, which has the highest correlation coefficient (0.9895). consists of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic feature, and one hydrophobic ali phatic feature. Hypol was further validated by test set and cross validation method. Then Hypol was used as a 3D query to screen several databases including Specs, NCI, Maybridge, and Chinese Nature Prod uct Database (CNPD). The hit compounds were subsequently subjected to filtering by Lipinskis rule of five and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, a total of 20 compounds were selected and have been shifted to in vitro and in vivo studies. As far as we know, this is the first report on the pharmacophore modeling even the first publicly reported virtual screening study of PLK1 inhibitors.
Pharmacophore modeling Virtual screening Polo-like kinase-1 Kinase inhibitor
Hui-Yuan Wang Zhi-Xing Cao Lin-Li Li Pei-Du Jiang Ying-Lan Zhao Shi-Dong Luo Li Yang Yu-Quan Wei Sheng-Yong Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School Wesf China School of pharmacy, Sichuan University, Sichuan 610041, China
国际会议
广州
英文
244-249
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）