School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Eur J Med Chem. 2023 Dec 5;261:115828. doi: 10.1016/j.ejmech.2023.115828. Epub 2023 Sep 25.
Kristen rat sarcoma (KRAS) is one of the most common oncogenes in human cancers. As a guanine nucleotide exchange factor, Son of Sevenless Homologue 1 (SOS1) represents a potential therapeutic concept for the treatment of KRAS-mutant cancers because of its activation on KRAS and downstream signaling pathways. In this review, we provide a comprehensive overview of the structure, biological function, and regulation of SOS1. We also focus on the recent advances in SOS1 inhibitors and emphasize their binding modes, structure-activity relationships and pharmacological activities. We hope that this publication can provide a comprehensive compendium on the rational design of SOS1 inhibitors.
KRAS 是人类癌症中最常见的致癌基因之一。作为鸟嘌呤核苷酸交换因子，SOS1 代表了治疗 KRAS 突变型癌症的潜在治疗概念，因为它能激活 KRAS 和下游信号通路。在这篇综述中，我们全面概述了 SOS1 的结构、生物学功能和调节。我们还重点介绍了 SOS1 抑制剂的最新进展，并强调了它们的结合模式、构效关系和药理活性。我们希望本出版物能为 SOS1 抑制剂的合理设计提供一个全面的纲要。
