Pharmacophore identification, docking and 鈥渋n silico鈥?screening for novel CDK1 inhibitors

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• 作者：Xiaowu Dong ; Jingying Yan ; Lilin Du ; Peng Wu ; Shufang Huang ; Tao Liu ; ^{lt601@zju.edu.cn} ; Yongzhou Hu ; ^{huyz@zju.edu.cn}
• 关键词：CDK1 inhibitors ; Pharmacophore ; HypoGen ; Homology modeling ; LigandFit
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：2012
• 期刊代码：77_10933263
• 类别：cp
• 出版时间：July, 2012
• 卷：37
• 期：Complete
• 页码：77-86
• 文件大小：1656 K

摘要

Pharmacophore models of cyclin-dependent kinase-1 (CDK1) inhibitors were established by using the Catalyst/HypoGen. The best pharmacophore model, Hypo1, consists of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), one hydrophobic (HY) and one ring aromatic (RA) feature. The validation results of Hypo1 through cost analysis, test set prediction, Fisher's cross method and receiver operating characteristic (ROC) study indicated that the Hypo1 was statistically valuable and reliable in identifying structural diverse CDK1 inhibitors. It is further supported by the consistent results from molecular docking studies. Finally, the Hypo1 was used to 鈥渋n silico鈥?screen the NCI and MayBridge database. The preferable hits obtained were further docked into ATP binding site of CDK1, and nine promising compounds were retrieved as novel potential CDK1 inhibitors for further studies.