组蛋白赖氨酸的甲基化在表观遗传调控中起着关键作用。组蛋白赖氨酸甲基化主要发生在H3的K4、K9、K27、K36、K79和H4的K20上,不同位点的甲基化修饰将导致转录激活或沉默。组蛋白赖氨酸甲基转移酶(HKMTs)和组蛋白赖氨酸去甲基化酶(HKDMs)共同调控着组蛋白赖氨酸的甲基化修饰状态。据报道,HKDMs的错误调控与多种肿瘤的发生和耐药有关,受到了更多的关注。因此,HKDMs抑制剂的研究开发意义重大,既可作为小分子探针研究其生物学功能,也有望开发为新型抗肿瘤药物。本文将对HKDMs抑制剂及其在疾病治疗方面的潜力进行综述。 Methylation of histone lysine plays a key role in epigenetic regulation. Histone lysine methylation mainly occurs on K20 of K4, K9, K27, K36, K79 and H4 of H3, and methylation modification at different sites will lead to transcriptional activation or silencing. Histone lysine methyltransferases (HKMTs) and histone lysine demethylase (HKDMs) together regulate the methylation status of histone lysine. It has been reported that the mis-regulation of HKDMs is associated with the development of multiple tumors and drug resistance, receiving more attention. Therefore, the research and development of HKDMs inhibitors are of great significance. They can not only be used as small molecule probes to study their biological functions, but also be developed as new antitumor drugs. This article reviews the potential of HKDMs inhibitors and their potential for treating diseases.