3D Pharmacophore Model Construction of Selective DPP-IV Inhibitors and Subsequent Validation and in Silico Screening of New Hits

作     者：Tianjiao Han~1 Yueqing Li~(1,*) Junfeng Gu~2 Zhi Cao~1 Weijie Zhao~1 Xicheng Wang~2 (1 School of Pharmaceutical Science and Technology,Dalian University of Technology,Dalian 116024, China 2 State Key Laboratory of Structure Analyses for Industrial Equipment,Dalian University of Technology,Dalian,116024,China) 

会议名称：《2011年全国药物化学学术会议——药物的源头创新》

会议日期：2011年

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

关 键 词：TypeⅡdiabetes Dipeptidyl-peptidaseⅣ Discovery Studio Pharmacophore model Database searching 

摘      要：正The 3D pharmacophore model of DPP-Ⅳinhibitors was established using the Discovery Studio software with the training set of 20 selective DPP-Ⅳ*** best pharmacophore hypothesis（Hypol） consists of one hydrogen-bond acceptor,one hydrophobic point,one positive ionizable feature,one aromatic ring as well as five excluded ***’s validation clearly shows that proposed Hypol has highly predictive ability and can be efficiently used as a 3D query for virtual screening to retrieve potential inhibitors from ZINC *** hit compounds subsequently were docked into the DPP-Ⅳactive site and 21 compounds were obtained based on PLP2 scoring ***,this study will be helpful to screen selective DPP-Ⅳinhibitors and provide scientific basis for de novo design of DPP-Ⅳinhibitors.