Cacace Angela, Banks Martyn, Spicer Timothy, Civoli Francesca, Watson John
Department of Lead Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA.
Drug Discov Today. 2003 Sep 1;8(17):785-92. doi: 10.1016/s1359-6446(03)02809-5.
G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.
G蛋白偶联受体（GPCRs）是迄今为止药物研发研究中最成功的靶蛋白。已鉴定出150多种具有潜在治疗意义的孤儿GPCRs，其激活配体或生物学功能尚不清楚。制药行业面临的最大挑战之一是将这些孤儿GPCRs与人类疾病联系起来。整合超高通量和聚焦筛选的高度自动化平行方法可用于鉴定孤儿GPCRs的小分子调节剂。然后，这些小分子可作为药理学工具，在人类疾病模型中探索孤儿受体的功能。在本综述中，我们描述了利用强大的超高通量筛选技术来鉴定孤儿GPCRs替代配体的方法。
