非肽类小分子趋化因子受体5拮抗剂的研究进展

Advances in research of non-peptide small-molecule CCR5 antagonists

趋化因子受体5(CCR5)属于G蛋白偶联受体超家族,是HIV感染早期介导病毒进入机体的主要辅助受体。CCR5拮抗剂已经成为一类重要的抗HIV病毒药物,主要包括趋化因子衍生物、非肽类小分子化合物、单克隆抗体、肽类化合物等4类。目前,全世界各大医药公司和研究机构纷纷研发了许多高选择性、活性强、生物利用度高的非肽类小分子CCR5拮抗剂,其中Maraviroc在2007年被FDA批准上市,还有一些目前已经进入临床试验阶段。文中对1999年到2009年10年间文献报道的相关非肽类小分子CCR5拮抗剂进行了综述。

CCR5,a membrane protein on cell surface,is a member of the G protein-coupled receptor superfamily and one of the major co-receptors for HIV-1 infection.CCR5 antagonists as viral entry inhibitors have recently emerged as an important class of anti-HIV medicines.Antagonists of CCR5 include following 4 types：chemokine derivatives,small molecule non-peptide compounds,monoclonal antibodies and peptides.In recent years,the major pharmaceutical companies and research institutions have developed a number of CCR5 antagonists with high selectivity,strong activity and a good bioavailability.Maraviroc was approved by FDA in 2007.The others have been under clinical trials.In this article,the literature from 1999 to 2009 related to non-peptide small-molecule CCR5 antagonists is reviewed.