文献类型：期刊文献

英文题名：Fragment-Based Drug Design and Drug Repositioning Using Multiple Ligand Simultaneous Docking (MLSD): Identifying Celecoxib and Template Compounds as Novel Inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3)

作者：Li, Huameng[1];Liu, Aiguo[3,4];Zhao, Zhenjiang[5];Xu, Yufang[5];Lin, Jiayuh[3];Jou, David[3];Li, Chenglong[1,2]

机构：[1]Ohio State Univ, Biophys Grad Program, Columbus, OH 43210 USA;[2]Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA;[3]Nationwide Childrens Hosp, Res Inst, Coll Med, Ctr Childhood Canc,Dept Pediat, Columbus, OH 43205 USA;[4]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Pediat, Wuhan 430030, Peoples R China;[5]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2011

卷号：54

期号：15

起止页码：5592

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000293419400029)】；

基金：The work was partially supported by a NIH R21 grant (Grant 1R21 CA 133652-01A1) to J.L. and C.L. and by the Ohio Supercomputer Center Glenn cluster computing resources.

语种：英文

摘要：We describe a novel method of drug discovery using MLSD and drug repositioning with cancer target STAT3 being used as a test case. Multiple drug scaffolds were simultaneously docked into hot spots of STAT3 by MLSD, followed by tethering to generate virtual template compounds. Similarity search of virtual hits on drug database identified celecoxib as a novel inhibitor of STAT3. Furthermore, we designed two novel lead inhibitors based on one of the lead templates and celecoxib.