2′-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine: A novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1
- 作者：Hyang-Min Byun ; Si Ho Choi ; Peter W. Laird ; Binh Trinh ; Maqbool A. Siddiqui ; Victor E. Marquez ; Allen S. Yang
- 关键词：DNA methylation ; Decitabine ; NPEOC-DAC ; Carboxylesterase ; DNA methyltransferase
- 刊名：Cancer Letters
- 出版年：2008
- 期刊代码：44_03043835
- 类别：med
- 出版时间：8 August 2008
- 卷：266
- 期：2
- 页码：238-248
- 文件大小：558 K
摘要
2′-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine (NPEOC-DAC), decitabine with a modification of the N4 position of the azacitidine ring can be used to inhibit DNA methyltransferase. This modification protects the azacitidine ring and can be cleaved by carboxylesterase to release decitabine. NPEOC-DAC was 23-fold less potent at low doses (<10 μM) than decitabine at inhibiting DNA methylation, and was also associated with a 3-day delay in its effect. However, at doses 
10 μM NPEOC-DAC was more effective at inhibiting DNA methylation. Theses differences between decitabine and NPEOC-DAC are dependent on the cleavage of the carboxylester bond, and could be potentially exploited pharmacologically.
10 μM NPEOC-DAC was more effective at inhibiting DNA methylation. Theses differences between decitabine and NPEOC-DAC are dependent on the cleavage of the carboxylester bond, and could be potentially exploited pharmacologically.