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通过调节RAS信号通路开发七号无翅型同源物1(SOS1)调节剂用于治疗癌症

Development of Son of Sevenless Homologue 1 (SOS1) Modulators To Treat Cancers by Regulating RAS Signaling.

作者信息

Luo Guangmei, Wang Bingrui, Hou Qiangqiang, Wu Xiaoxing

机构信息

Department of Medicinal Chemistry, School of Pharmacy and Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China.

出版信息

J Med Chem. 2023 Apr 13;66(7):4324-4341. doi: 10.1021/acs.jmedchem.2c01729. Epub 2023 Mar 28.

Abstract

Son of sevenless homologue 1 (SOS1) protein is universally expressed in cells and plays an important role in the RAS signaling pathway. Specifically, this protein interacts with RAS in response to upstream stimuli to promote guanine nucleotide exchange in RAS and activates the downstream signaling pathways. Thus, targeting SOS1 is a new approach for treating RAS-driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of SOS1 and focus on recent advances in the discovery of activators, inhibitors, and PROTACs that target SOS1. This review aims to provide a timely and updated overview on the strategies for targeting SOS1 in cancer therapy.

摘要

七号无翅型同源物1(SOS1)蛋白在细胞中广泛表达,在RAS信号通路中发挥重要作用。具体而言,该蛋白响应上游刺激与RAS相互作用,促进RAS中的鸟嘌呤核苷酸交换并激活下游信号通路。因此,靶向SOS1是治疗RAS驱动型癌症的一种新方法。在这篇观点文章中,我们简要总结了SOS1的结构和功能方面,并重点关注靶向SOS1的激活剂、抑制剂和蛋白降解靶向嵌合体(PROTAC)的最新发现进展。本综述旨在及时更新关于癌症治疗中靶向SOS1策略的概述。

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