Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Quantitative Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Br J Pharmacol. 2018 Nov;175(21):4060-4071. doi: 10.1111/bph.14157. Epub 2018 Mar 25.
One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour.
This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
现代药物发现的一种方法是通过调节 GPCR 的活性，来识别增强或减弱各种细胞类型和组织中信号转导级联的试剂。这一策略已促成了许多疾病治疗药物的开发，包括心血管疾病、精神障碍、HIV/AIDS、某些类型的癌症和 2 型糖尿病（T2DM）。这些成功证明了进一步将 GPCR 作为疾病靶点的合理性，并提供了有助于指导确定未来治疗剂的关键经验。本报告重点讨论了 GPCR 药物发现的现状，强调了开发治疗 T2DM 和肥胖症的新分子的努力。我们根据导致这一努力成功和失败的因果因素，分析了历史上为治疗代谢疾病而产生基于 GPCR 的药物的努力。
本文是 GPCR 分子药理学专题的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
