AUTHOR=Zhou Xikun , Wu Mingbo , Xie Yongmei , Li Guo-Bo , Li Tao , Xie Rou , Wang Kailun , Zhang Yige , Zou Chaoyu , Wu Wenling , Wang Qi , Wang Xiangwei , Zhang Ximu , Li Jiong , Li Jing , Wei Yu-Quan TITLE=Identification of Glycine Receptor α3 as a Colchicine-Binding Protein JOURNAL=Frontiers in Pharmacology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01238 DOI=10.3389/fphar.2018.01238 ISSN=1663-9812 ABSTRACT=

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations.