DNA甲基转移酶(DNMT)在基因组DNA甲基化中起着至关重要的作用。在哺乳动物中,DNMT调节胚胎和成体细胞DNA甲基化的动态模式。DNMT的功能异常通常表明癌症,包括肿瘤抑制基因(TSG)的整体低甲基化和部分高甲基化,加速肿瘤的恶性,使病人的病情恶化,并显著加剧癌症治疗的难度。目前,核苷DNMT抑制剂如氮杂胞苷和地西他滨已被FDA和EMA批准用于治疗急性髓性白血病(AML),慢性粒单核细胞白血病(CMML),骨髓增生异常综合征(MDS)。因此,靶向DNMT是一种非常有前途的抗肿瘤策略。本文就DNMT抑制剂对肿瘤的治疗作用作一综述。旨在通过发现更多具有高活性的DNMT抑制剂,为癌症的治疗提供更多的可能性。高选择性,以及未来良好的药物特性。
DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of
cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on
cancers. It aims to provide more possibilities for the treatment of
cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.