title: 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).
abstract: 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.
authors.affiliation: Biophysics Graduate Program, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Huameng
authors.initials: H
authors.lastname: Li
authors.forename: Aiguo
authors.initials: A
authors.lastname: Liu
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Jou
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
mesh_terms: D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D058492:Drug Repositioning; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000068579:Celecoxib; D011720:Pyrazoles; D050796:STAT3 Transcription Factor; D013449:Sulfonamides; D000093242:Interleukin-6 Inhibitors