K-RAS^(G12C)小分子共价抑制剂的研究进展

Recent progress of covalent small-molecule inhibitors of K-RAS

Ras原癌基因的突变是人类癌症中最常见的激活突变,驱动人类30%肿瘤的发生与发展,因此人们一直希望能够研发出靶向RAS蛋白的抗肿瘤药物,但进展缓慢。直至最近两年,随着首个K-RASG12C共价抑制剂AMG-510进入临床试验,直接靶向RAS蛋白的药物研发才逐渐显露出希望的曙光。本文主要介绍K-RASG12C小分子共价抑制剂的研发历程、临床前研究、临床试验以及RAS靶向药物未来的发展方向。

Rat sarcoma viral oncogene homolog(Ras) mutation is the most common activation mutation in human cancer,which promotes the occurrence and development of 30% human cancer.Many scholars have always hoped to develop anti-tumor drugs targeting RAS proteins,but progressed slow.Until the last two years,as the first K-RASG12 C covalent inhibitor AMG-510 entered clinical trials,the development of drugs that directly target the RAS protein gradually showed the dawn of hope.This review highlights the discovery process,the preclinical and clinical results,and the combination regimen of K-RASG12 C small molecule covalent inhibitors.