GPR35 as a Novel Therapeutic Target.
GPR35 as a Novel Therapeutic Target.
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DOI：
10.3389/fendo.2011.00068
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发表时间：
2011
影响因子：
5.2
通讯作者：
Milligan G
中科院分区：
文献类型：
--
作者：
Mackenzie AE;Lappin JE;Taylor DL;Nicklin SA;Milligan G
G蛋白偶联受体（GPCR）仍然是研究最好的一类细胞表面受体和最易处理的蛋白质家族的新的小分子药物的发现。尽管如此，相当数量的GPCR仍然表征不佳，并且在相当数量的情况下，激活它们的内源性配体仍然不确定或具有可疑的生理相关性。GPR 35最初是在十多年前发现的，但一直是一种“孤儿”受体。最近的出版物突出了新的配体，内源性产生的和合成的，这表明在这种受体的显着效力。此外，越来越多的证据强调了GPR 35在疾病中的潜在作用，因此，更全面地表征GPR 35并将其开发为从糖尿病和高血压到哮喘的新型治疗靶点的努力正在增加。最近鉴定的配体显示出明显的物种选择性，表明未来药物开发的主要挑战。当我们开始理解这些问题时，鉴定GPR 35的新型激动剂和拮抗剂配体的持续努力将有助于破译其真正的生理学相关性;将多种体外测定系统转化为体内动物疾病系统，并最终转化为人类。
G protein-coupled receptors (GPCRs) remain the best studied class of cell surface receptors and the most tractable family of proteins for novel small molecule drug discovery. Despite this, a considerable number of GPCRs remain poorly characterized and in a significant number of cases, endogenous ligand(s) that activate them remain undefined or are of questionable physiological relevance. GPR35 was initially discovered over a decade ago but has remained an “orphan” receptor. Recent publications have highlighted novel ligands, both endogenously produced and synthetic, which demonstrate significant potency at this receptor. Furthermore, evidence is accumulating which highlights potential roles for GPR35 in disease and therefore, efforts to characterize GPR35 more fully and develop it as a novel therapeutic target in conditions that range from diabetes and hypertension to asthma are increasing. Recently identified ligands have shown marked species selective properties, indicating major challenges for future drug development. As we begin to understand these issues, the continuing efforts to identify novel agonist and antagonist ligands for GPR35 will help to decipher its true physiological relevance; translating multiple assay systems in vitro, to animal disease systems in vivo and finally to man.