Son of Sevenless (SOS) is a guanine nucleotide exchange factor that activates the important cell signaling switch KRAS. SOS acts as a pacemaker for KRAS, the beating heart of cancer, by catalyzing the "beating" from the KRAS(off) to the KRAS(on) conformation. Activating mutations in SOS1 are common in Noonan syndrome and oncogenic alterations in KRAS drive 1 in seven human cancers. Promising clinical efficacy has been observed for selective KRASG12C inhibitors, but the vast majority of oncogenic KRAS alterations remain undrugged. The discovery of a druggable pocket on SOS1 has led to potent SOS1 inhibitors such as BI-3406. SOS1 inhibition leads to antiproliferative effects against all major KRAS mutants. The first SOS1 inhibitor has entered clinical trials for KRAS-mutated cancers. In this review, we provide an overview of SOS1 function, its association with cancer and RASopathies, known SOS1 activators and inhibitors, and a future perspective is provided.

中文翻译：

---

瞄准无七之子 1：KRAS 的起搏器。

Sevenless 之子 (SOS) 是一种鸟嘌呤核苷酸交换因子，可激活重要的细胞信号开关 KRAS。SOS 通过催化从 KRAS(off) 到 KRAS(on) 构象的“跳动”，充当 KRAS（癌症跳动的心脏）的心脏起搏器。SOS1 中的激活突变在 Noonan 综合征中很常见，而 KRAS 的致癌改变是 7 种人类癌症中的一种。已经观察到选择性 KRASG12C 抑制剂具有有希望的临床疗效，但绝大多数致癌 KRAS 改变仍未得到药物治疗。在 SOS1 上发现了可成药的口袋，从而产生了有效的 SOS1 抑制剂，例如 BI-3406。SOS1 抑制导致对所有主要 KRAS 突变体的抗增殖作用。第一个 SOS1 抑制剂已进入 KRAS 突变癌症的临床试验。在这篇评论中，我们概述了 SOS1 功能，