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.

克里斯汀大鼠肉瘤（KRAS）是人类癌症中最常见的癌基因之一。作为一种鸟嘌呤核苷酸交换因子，Son of Sevenless Homologue 1 (SOS1) 由于其对 KRAS 和下游信号通路的激活，代表了治疗 KRAS 突变癌症的潜在治疗概念。在这篇综述中，我们全面概述了 SOS1 的结构、生物学功能和调控。我们还关注SOS1抑制剂的最新进展，并强调它们的结合模式、构效关系和药理活性。我们希望本出版物能够为 SOS1 抑制剂的合理设计提供全面的概要。