DNA甲基化过程广泛存在于哺乳动物细胞内，在表观遗传修饰和染色质稳定性中都起着关键的作用。DNA高甲基化修饰通常在肿瘤发展的进程中有着重要影响。guadecitabine是由Astex公司研发的新型的DNA甲基转移酶抑制剂。作为地西他滨的前药，guadecitabine在体内经磷酸酯酶水解得到地西他滨，掺入DNA链中，与DNA甲基转移酶共价结合，不可逆地抑制DNA甲基化过程。临床研究表明，guadecitabine在针对骨髓增生异常综合征和急性骨髓性白血病等肿瘤的治疗中具有明显的有效性和安全性。

DNA methylation processes are widely found in mammalian cells. It plays a key role in epigenetic modification and chromatin stability. DNA hypomethylation usually accelerates the progress of tumors. Guadecitabine is a novel DNA methyltransferase inhibitor launched by Astex. As the pro-drug of dicitabine, guadecitabinehydrolyzed intodicitabine by phosphoesterase, incorporates into DNA chains and covalently binds with DNA methylation methyltransferase, which inhibits DNA methylation irreversibly. Clinical studies have shown that guadecitabine has significant potency and safety on myelodysplastic syndromes and acute myeloid leukemia.

中国医学科学院医学与健康科技创新工程经费资助项目