School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Trends Pharmacol Sci. 2023 May;44(5):263-273. doi: 10.1016/j.tips.2023.03.001. Epub 2023 Mar 30.
The orphan G-protein-coupled receptor 35 (GPR35), although poorly characterised, is attracting considerable interest as a therapeutic target. Marked differences in pharmacology between human and rodent orthologues of the receptor and a dearth of antagonists with affinity for mouse and rat GPR35 have previously restricted the use of preclinical disease models. The development of improved ligands, novel transgenic knock-in mouse lines, and detailed analysis of the disease relevance of single-nucleotide polymorphisms (SNPs) have greatly enhanced understanding of the key roles of GPR35 and have stimulated efforts towards disease-targeted proof-of-concept studies. In this opinion article, new information on the biology of the receptor is considered, whilst insight into how GPR35 is currently being assessed for therapeutic utility - in areas ranging from inflammatory bowel diseases to nonalcoholic steatohepatitis and various cancers - is also provided.
孤儿 G 蛋白偶联受体 35（GPR35）虽然特征不明显，但作为治疗靶点引起了相当大的关注。受体的人和啮齿动物同源物之间的药理学存在显著差异，并且缺乏对小鼠和大鼠 GPR35 具有亲和力的拮抗剂，这以前限制了临床前疾病模型的使用。改进配体的开发、新型转基因敲入小鼠系以及对单核苷酸多态性（SNP）疾病相关性的详细分析，极大地增强了对 GPR35 关键作用的理解，并促使人们努力开展针对疾病的概念验证研究。在这篇观点文章中，考虑了受体生物学的新信息，同时还介绍了 GPR35 目前如何在从炎症性肠病到非酒精性脂肪性肝炎和各种癌症等各个领域评估其治疗用途的情况。
