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)
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.
基金：
NIH [1R21 CA 133652-01A1]; Ohio Supercomputer Center Glenn cluster computing resources
第一作者单位：[1]Ohio State Univ, Biophys Grad Program, Columbus, OH 43210 USA
通讯作者：
通讯机构：[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
推荐引用方式(GB/T 7714)：
Li Huameng,Liu Aiguo,Zhao Zhenjiang,et al.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)[J].JOURNAL OF MEDICINAL CHEMISTRY.2011,54(15):5592-5596.doi:10.1021/jm101330h.
APA：
Li, Huameng,Liu, Aiguo,Zhao, Zhenjiang,Xu, Yufang,Lin, Jiayuh...&Li, Chenglong.(2011).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).JOURNAL OF MEDICINAL CHEMISTRY,54,(15)
MLA：
Li, Huameng,et al."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)".JOURNAL OF MEDICINAL CHEMISTRY 54..15(2011):5592-5596
医学