文献类型：期刊文献

英文题名：Discovering Potent Small Molecule Inhibitors of Cyclophilin A Using de Novo Drug Design Approach

作者：Ni, Shuaishuai[3];Yuan, Yaxia[1,2];Huang, Jin[3];Mao, Xiaona[3];Lv, Maosheng[3];Zhu, Jin[3];Shen, Xu[3,4];Pei, Jianfeng[1,2];Lai, Luhua[1,2];Jiang, Hualiang[3,4];Li, Jian[3]

机构：[1]Peking Univ, Coll Chem & Chem Engn, Coll Chem,BNLMS, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China;[2]Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China

年份：2009

卷号：52

期号：17

起止页码：5295

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000269655500002)】；

基金：We gratefully acknowledge Professor Wei Wang (University of New Mexico) for revising manuscript, and the financial support from the National Natural Science Foundation of China (grant 90813005), the 863 Hi-Tech Program of China (grant 2006AA020400, 2006AA02Z337, 2007-AA02Z147), the China 111 Project (grant B07023), Shanghai Rising-Star Program (A type, grant 07QA14013), and Shanghai Pujiang Program (D type, grant PJ200700247).

语种：英文

摘要：This work describes an integrated approach of de novo drug design, chemical synthesis, and bioassay for quick identification of a series of novel small molecule cyclophilin A (CypA) inhibitors (1-3). The activities or the two most potent CypA inhibitors (3h and 3i) are 2.59 and 1.52 nM, respectively, which are about 16 and 27 times more potent than that of cyclosporin A. This study clearly demonstrates the power of our de novo drug design strategy and the related program LigBuilder 2.0 in drug discovery.