研究动态
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GPR35: 从谜团到治疗靶点。

GPR35: from enigma to therapeutic target.

发表日期:2023 Mar 30
作者: Graeme Milligan
来源: Disease Models & Mechanisms

摘要:

孤儿G蛋白偶联受体35(GPR35)虽然特征不明确,但作为治疗靶点引起了相当大的兴趣。由于受体在人和啮齿动物中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,因此先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单核苷酸多态性(SNP)的疾病相关性的详细分析极大地增强了对GPR35关键作用的了解,并激发了针对疾病的概念证明研究的努力。在这篇观点文章中,将考虑有关受体生物学的新信息,同时还提供有关如何评估GPR35在范围从炎症性肠病到非酒精性脂肪性肝炎和各种癌症的治疗效用的洞察力。opyright © 2023 Elsevier Ltd.保留所有权利。
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.Copyright © 2023 Elsevier Ltd. All rights reserved.