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阿扎胞苷(azacitidine)于2004-05-19被美国食品药品监督管理局(FDA)批准上市,是第一个被批准用于骨髓增生异常综合征(MDS)的表观遗传学修饰治疗药物。近年发现,DNA过度甲基化(hypermethylation)可使包括p15INK4b、p21、CALC1、E-cadherin、HIC-1、RASSFIA等多种调控正常细胞生长、分化及凋亡的基因表达受到抑制,从而导致MDS的发病。因此,DNA的去甲基化治疗已经成为MDS的一个重要治疗靶点[1]。作为一种胞嘧啶核苷类似物,阿扎胞苷在DNA复制时可与DNA甲基转移酶(DNMT)竞争性结合,抑制细胞中新合成DNA的甲基化,从而恢复多种与细胞增殖
Azacitidine was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2004 and is the first epigenetic modified drug approved for myelodysplastic syndrome (MDS). . In recent years, it has been found that hypermethylation of DNA can inhibit the expression of many genes that regulate the growth, differentiation and apoptosis of normal cells including p15INK4b, p21, CALC1, E-cadherin, HIC-1 and RASSFIA, The incidence. Therefore, demethylation of DNA has become an important therapeutic target for MDS [1]. As a cytidine analog, azacitidine competes with DNA methyltransferase (DNMT) for DNA replication and inhibits methylation of newly synthesized DNA in cells, thereby restoring a wide range of cellular responses to cell proliferation