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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 occurs extensively in mammalian cells and plays a key role in epigenetic modification and chromatin stability. DNA hypermethylation often plays a significant role in the process of tumor development. guadecitabine is a new type of DNA methyltransferase inhibitor developed by Astex. As a prodrug of decitabine, guadecitabine is hydrolyzed by phosphatase in vivo to decitabine, incorporated into DNA strands, covalently bound to DNA methyltransferases, and irreversibly inhibit DNA methylation. Clinical studies have shown that guadecitabine has obvious efficacy and safety in the treatment of tumors such as myelodysplastic syndrome and acute myeloid leukemia.