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Epigenetic drug discovery: a success story for cofactor interference
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Epigenetic drug discovery: a success story for cofactor interference
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Journal Article
Epigenetic drug discovery: a success story for cofactor interference
2018
Overview
Within the past two decades, seven epigenetic drugs have received regulatory approval and numerous other candidates are currently in clinical trials. Among the epigenetic targets are the writer and eraser enzymes that are, respectively, responsible for the reversible introduction and removal of structural modifications in the nucleosome. This review discusses the progress achieved in the design and development of inhibitors against the key writer and eraser pairs: DNA methyltransferases and Tet demethylases; lysine/arginine methyltransferases and lysine demethylases; and histone acetyltransferases and histone deacetylases. A common theme for the successful inhibition of these enzymes in a potent and selective manner is the targeting of the cofactors present in the active site, namely zinc and iron cations, S-adenosylmethione, nicotinamide adenine dinucleotide, flavin adenine dinucleotide and acetyl Coenzyme A.
This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
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