GPR35去孤儿化研究及其在疾病中的作用  

Recent advances in deorphanization of GPR35 and its functions in related diseases

作　　者：张启情 焦宇 张尊建[1] 许风国[1] 张培[1] ZHANG Qi-qing;JIAO Yu;ZHANG Zun-jian;XU Feng-guo;ZHANG Pei(Ministry of Education Key Laboratory of Drug Quality Control and Pharmacovigilance,China Pharmaceutical University,Nanjing 210009,China;School of Science,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学,药物质量与安全预警教育部重点实验室,江苏南京210009 [2]中国药科大学理学院,江苏南京211198

出　　处：《药学学报》2023年第8期2139-2145,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82073812,82104117,82173947,82273896);江苏省自然科学基金项目(BK20210427).

摘　　要：G蛋白偶联受体(G protein-coupled receptors,GPCRs)是药物研发中最受关注的靶点家族,尚存在近300种孤儿受体,具有重大潜在药物研发价值。G蛋白偶联受体35(G protein-coupled receptor 35,GPR35)是一种A类、视紫红质样孤儿GPCR,广泛参与胃肠道疾病、心血管疾病和癌症等多种疾病的发生发展,并与免疫调节密切相关,提示其可作为多种疾病治疗潜在靶点。然而,目前针对GPR35的研究尚不充分,包括GPR35真正的内源性配体尚未确证,其在疾病中发挥作用的分子机制仍不完全清楚,缺乏靶向GPR35的有效干预策略等。本文综述了GPR35去孤儿化研究、GPR35相关信号通路及其与多种疾病的关联,以期为深入研究GPR35在疾病中的作用、研发靶向GPR35的药物提供参考。G protein-coupled receptors(GPCRs)represent the largest family of membrane proteins and are the target of approximately half of all therapeutic drugs.There are~300 orphan GPCRs,which have great potential in drug development.G protein-coupled receptor 35(GPR35),a rhodopsin-like orphan GPCR,is widely involved in immune regulation,gastrointestinal disorders,cardiovascular diseases,cancer,as well as other diseases,suggesting its great potential as a therapeutic target in a variety of diseases.However,the current research on GPR35 is insufficient,including the true endogenous ligand has not been confirmed,the molecular mechanism of its role in disease is not fully understood,and there is a lack of effective intervention strategies targeting GPR35.This article summarizes the deorphatization of GPR35,GPR35-related signaling pathways and their association with various diseases,in order to provide a reference for in-depth study of GPR35 in diseases and development of drugs targeting GPR35.

关 键 词：G蛋白偶联受体35 孤儿受体 胃肠道疾病 心血管疾病 癌症 

分 类 号：R966[医药卫生—药理学]