2'-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine: a novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1.
Cancer Lett
; 266(2): 238-48, 2008 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-18499340
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
/
Pró-Fármacos
/
Hidrolases de Éster Carboxílico
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DNA-Citosina Metilases
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Antimetabólitos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos