Issue 3, 2012

Small molecules DNAmethyltransferasesinhibitors


Methylation catalyzed by the DNAmethyltransferases affects the C5 position of cytosine residues in DNA. This physiological process is active from the embryo conception, throughout all its developmental steps, and also later for the maintenance of the adult organism. Excess methylated cytosine in tumor suppressor genes is a consistent hallmark of human cancers. However, DNA methylation variation is now acknowledged to significantly contribute to genetic and common diseases. DNAmethyltransferases became attractive therapeutic targets as DNA demethylation, in vitro, brought cancer cell differentiation and apoptosis. Inhibitors are already in use, alone or in combination, to treat myeloid malignancies, while clinical assays are ongoing for other diseases. DNA methylation and histone modifications are intimately correlated with epigenetic heritable modifications of gene expression that are independent of changes in the genetic sequence. Common initiatives for epigenetic research have built public databases with useful resources. The recent discovery of 5-hydroxymethyl cytosine has added new questions and challenges for the epigenome community. We review here knowledge about DNA methylation to provide researchers with the information needed to make more active inhibitors for the benefit of patients. Because of space limitations, many important works cannot be cited. We refer the reader to reviews containing these references.

Graphical abstract: Small molecules DNA methyltransferases inhibitors

Article information

Article type
Review Article
29 Jul 2011
31 Aug 2011
First published
21 Oct 2011

Med. Chem. Commun., 2012,3, 263-273

Small molecules DNAmethyltransferasesinhibitors

N. Martinet, B. Y. Michel, P. Bertrand and R. Benhida, Med. Chem. Commun., 2012, 3, 263 DOI: 10.1039/C1MD00194A

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