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Cancer Lett. 2008 Aug 8;266(2):238-48. doi: 10.1016/j.canlet.2008.02.069. Epub 2008 May 21.

2'-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine: a novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1.

Author information

1
Division of Hematology, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Room 6428, Los Angeles, CA, USA.

Abstract

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 (<10microM) than decitabine at inhibiting DNA methylation, and was also associated with a 3-day delay in its effect. However, at doses > or = 10microM 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.

PMID:
18499340
PMCID:
PMC2528876
DOI:
10.1016/j.canlet.2008.02.069
[Indexed for MEDLINE]
Free PMC Article

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