Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Trends Pharmacol Sci. 2013 May;34(5):290-8. doi: 10.1016/j.tips.2013.02.006. Epub 2013 Apr 1.
G-Protein-coupled receptors (GPCRs) signal through G protein α and βγ subunit families to regulate a wide range of physiological and pathophysiological processes. As such, GPCRs are major targets for therapeutic drugs. Downstream targets of GPCRs have also gained interest as a therapeutic approach to complex pathologies involving multiple GPCRs. One such approach involves targeting of the G proteins themselves. Several small molecule Gα and Gβγ modulators have been developed and been tested in various animal models of disease. Here we will discuss the requirements for targeting Gα and Gβγ subunits, the mechanisms of action of currently identified inhibitors, and focus on the potential utility of Gα and Gβγ inhibitors in the treatment of various cancers.
G 蛋白偶联受体 (GPCRs) 通过 G 蛋白α 和βγ亚基家族传递信号，调节广泛的生理和病理生理过程。因此，GPCR 是治疗药物的主要靶点。GPCR 的下游靶点也作为一种治疗涉及多种 GPCR 的复杂疾病的方法引起了关注。一种这样的方法涉及到靶向 G 蛋白本身。已经开发了几种小分子 Gα 和 Gβγ调节剂，并在各种疾病动物模型中进行了测试。在这里，我们将讨论靶向 Gα 和 Gβγ 亚基的要求、目前鉴定的抑制剂的作用机制，并重点介绍 Gα 和 Gβγ 抑制剂在治疗各种癌症中的潜在应用。
