KRASG12C已被确定为固体肿瘤治疗的潜在靶点。人类癌症最常转化的蛋白质之一是小 Kirsten 鼠肉瘤同源物（KRAS）GTP酶的亚单位，通常是癌基因驱动因子。KRASG12C被改变以保持蛋白质处于活性GTP结合形态。长期以来，KRAS一直被视为“不可药用”的靶点，但聚焦于KRASG12C突变的蛋氨酸的持续研究努力取得了很有前途的结果。例如，美国食品药品监督管理局已经通过了Sotorasib和Adagrasib的紧急批准，用于治疗转移性肺癌。这样的成就激发了对KRASG12C的几种原创方法。在本文中，我们关注KRASG12C抑制剂的设计、开发和历史。 版权所有 © 2023 Elsevier Ltd.

KRASG12C has been identified as a potential target in the treatment of solid tumors. One of the most often transformed proteins in human cancers is the small Kirsten rat sarcoma homolog (KRAS) subunit of GTPase, which is typically the oncogene driver. KRASG12C is altered to keep the protein in an active GTP-binding form. KRAS has long been considered an 'undrugable' target, but sustained research efforts focusing on the KRASG12C mutant cysteine have achieved promising results. For example, the US Food and Drug Administration (FDA) has passed emergency approval for sotorasib and adagrasib for the treatment of metastatic lung cancer. Such achievements have sparked several original approaches to KRASG12C. In this review, we focus on the design, development, and history of KRASG12C inhibitors.Copyright © 2023 Elsevier Ltd. All rights reserved.