Heterotrimeric G Proteins as Therapeutic Targets in Drug Discovery.,Journal of Medicinal Chemistry

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Heterotrimeric G Proteins as Therapeutic Targets in Drug Discovery.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2019-12-16 , DOI: 10.1021/acs.jmedchem.9b01452
Jian Li ₁ , Yang Ge ₁ , Jun-Xiang Huang ₁ , Kristian Strømgaard ₂ , Xiaolei Zhang ₁ , Xiao-Feng Xiong ₁

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Heterotrimeric G proteins are molecular switches in GPCR signaling pathways and regulate a plethora of physiological and pathological processes. GPCRs are efficient drug targets, and more than 30% of the drugs in use target them. However, selectively targeting an individual GPCR may be undesirable in various multifactorial diseases in which multiple receptors are involved. In addition, abnormal activation or expression of G proteins is frequently associated with diseases. Furthermore, G proteins harboring mutations often result in malignant diseases. Thus, targeting G proteins instead of GPCRs might provide alternative approaches for combating these diseases. In this review, we discuss the biochemistry of heterotrimeric G proteins, describe the G protein-associated diseases, and summarize the currently known modulators that can regulate the activities of G proteins. The outlook for targeting G proteins to treat diverse diseases is also included in this manuscript.

中文翻译：

异三聚体G蛋白作为药物发现中的治疗靶标。

异三聚体G蛋白是GPCR信号通路中的分子开关，可调节大量的生理和病理过程。GPCR是有效的药物靶标，使用的药物中有30％以上是针对它们的。但是，在涉及多个受体的多种多因素疾病中，选择性靶向单个GPCR可能是不希望的。另外，G蛋白的异常激活或表达通常与疾病有关。此外，具有突变的G蛋白经常导致恶性疾病。因此，靶向G蛋白而不是GPCR可能会提供对抗这些疾病的替代方法。在这篇综述中，我们讨论了异源三聚体G蛋白的生物化学，描述了G蛋白相关疾病，并总结了目前已知的可以调节G蛋白活性的调节剂。该手稿还涉及靶向G蛋白以治疗多种疾病的前景。

更新日期：2019-12-16

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