DNA甲基化過(guò)程廣泛存在于哺乳動(dòng)物細(xì)胞內(nèi)，在表觀遺傳修飾和染色質(zhì)穩(wěn)定性中都起著關(guān)鍵的作用。DNA高甲基化修飾通常在腫瘤發(fā)展的進(jìn)程中有著重要影響。guadecitabine是由Astex公司研發(fā)的新型的DNA甲基轉(zhuǎn)移酶抑制劑。作為地西他濱的前藥，guadecitabine在體內(nèi)經(jīng)磷酸酯酶水解得到地西他濱，摻入DNA鏈中，與DNA甲基轉(zhuǎn)移酶共價(jià)結(jié)合，不可逆地抑制DNA甲基化過(guò)程。臨床研究表明，guadecitabine在針對(duì)骨髓增生異常綜合征和急性骨髓性白血病等腫瘤的治療中具有明顯的有效性和安全性。

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.

中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)學(xué)與健康科技創(chuàng)新工程經(jīng)費(fèi)資助項(xiàng)目