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
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
School of Bioscience and Biotechnology, Chengdu Medical College, Chengdu, China.
Front Pharmacol. 2018 Nov 8;9:1238. doi: 10.3389/fphar.2018.01238. eCollection 2018.
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.
秋水仙碱（Col）被认为是一种预防和治疗急性痛风发作（ flare ）的高效生物碱。然而，关于秋水仙碱在疼痛治疗中的潜在机制知之甚少。我们之前开发了一种定制的虚拟靶点识别方法，称为IFPTarget，用于小分子靶点识别。在本研究中，通过使用IFPTarget和配体相似性整合方法（SEA），我们表明在炎性疼痛处理中起关键作用的甘氨酸受体α3（GlyRα3）是秋水仙碱的潜在靶点。此外，使用合成的Col-生物素缀合物（通过聚乙二醇连接秋水仙碱和生物素）进行免疫沉淀和生物层干涉测量分析确定，秋水仙碱直接与GlyRα3结合。这些结果表明，GlyRα3可能介导秋水仙碱诱导的炎性疼痛抑制。然而，GlyRα3是否是秋水仙碱的功能性靶点以及是否作为痛风性关节炎的潜在治疗靶点，还需要进一步研究。
