会议专题

A Specific Pharmacophore Model of Aurora B Kinase Inhibitors and Virtual Screening Studies Based on it

In this study, 3D-pharmacophore models of Aurora B kinase inhibitors have been developed by using HipHop and HypoGen modules in Catalyst software package. The best pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9911), consists of one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic aliphatic moiety and one ring aromatic feature. Hypo1 was validated by test set and cross-validation methods. And the specificity of Hypol to Aurora B inhibitors was examined with the use of selective inhibitors against Aurora B and its paralogue Aurora A. The results clearly indicate that Hypol can differentiate selective inhibitors of Aurora B from those of Aurora A, and the ring aromatic feature likely plays some important roles for the specificity of Hypol. Then Hypol was used as a 3D query to screen several databases including Specs, NCI, Maybridge and Chinese Nature Product Database (CNPD) for identifying new inhibitors of Aurora B. The hit compounds were subsequently subjected to filtering by Lipinskis rule of five and docking studies to refine the retrieved hits, and some compounds selected from the top ranked hits have been suggested for further experimental assay studies.

Hui-Yuan Wang Lin-Li Li Zhi-Xing Cao Shi-Dong Luo Yu-Quan Wei Sheng-Yong Yang

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School West China School of pharmacy, Sichuan University, Sichuan 610041, China State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School

国际会议

The 5th International Conference of Molecular Simulations and Applied Informatics Technologies(第五届国际分子模拟与信息技术应用学术会议 ICMS&I)

武汉

英文

78-89

2010-09-01(万方平台首次上网日期,不代表论文的发表时间)