Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity.
PLoS One
; 9(5): e96941, 2014.
Article
em En
| MEDLINE
| ID: mdl-24810902
ABSTRACT
Chemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compounds, when tested at sub-toxic doses, induced the luciferase re-expression in a stable construct controlled by a cytomegalovirus (CMV) promoter silenced by methylation (CMV-luc assay). Finally, in human lymphoma U-937 and RAJI cells, the N-(1-benzylpiperidin-4-yl)-2-(4-phenylpiperazin-1-yl)quinazolin-4-amine induced the highest proliferation arrest and cell death induction starting from 10 µM, in agreement with its DNMT3A inhibitory potency.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Azepinas
/
Histona-Lisina N-Metiltransferase
/
DNA (Citosina-5-)-Metiltransferases
/
Inibidores Enzimáticos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article