Cancer remains the most serious disease that threatens human health. Molecularly targeted cancer therapies, specifically small-molecule protein kinase inhibitors, form an important part of cancer therapy. Targeted covalent modification represents a proven approach to drug discovery with the recent FDA approvals of afatanib, ibrutinib, and osimertinib agents, which were designed to undergo an irreversible hetero-Michael addition reaction with a unique cysteine residue of a specific protein. Covalent inhibitors possess numerous advantages, including increased biochemical efficacy, longer duration of action, the high potential for improved therapeutic index due to lower effective dose, and the potential to inhibit certain drug resistance mechanisms. In this regard, the novel targeted anticancer agents whose activity is presumably dependent upon a hetero-Michael addition reaction with thiols are summarized in this article.

癌症仍然是威胁人类健康的最严重疾病。分子靶向癌症疗法，特别是小分子蛋白激酶抑制剂，是癌症疗法的重要组成部分。有针对性的共价修饰代表了一种可靠的药物发现方法，最近有FDA批准afatanib，ibrutinib和osimertinib药物，这些药物旨在与特定蛋白质的独特半胱氨酸残基发生不可逆的异Michael加成反应。共价抑制剂具有许多优点，包括增加的生化功效，更长的作用持续时间，由于较低的有效剂量而具有改善治疗指数的高潜力以及抑制某些耐药机制的潜力。在这方面，