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Properly Substituted Analogues of BIX-01294 Lose Inhibition of G9a Histone Methyltransferase and Gain Selective Anti-DNA Methyltransferase 3A Activity

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03182293
Contributor : Marie-Ange Garnier <>
Submitted on : Friday, March 26, 2021 - 11:36:54 AM
Last modification on : Tuesday, March 30, 2021 - 3:48:52 PM
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Dante Rotili, Domenico Tarantino, Biagina Marrocco, Christina Gros, Véronique Masson, et al.. Properly Substituted Analogues of BIX-01294 Lose Inhibition of G9a Histone Methyltransferase and Gain Selective Anti-DNA Methyltransferase 3A Activity. PLoS ONE, Public Library of Science, 2014, 9 (5), pp.e96941. ⟨10.1371/journal.pone.0096941⟩. ⟨pasteur-03182293⟩

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