Journal of medicinal and pharmaceutical chemistry 2008-11-27

Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases.

Nathan R Rose, Stanley S Ng, Jasmin Mecinović, Benoît M R Liénard, Simon H Bello, Zhe Sun, Michael A McDonough, Udo Oppermann, Christopher J Schofield

Index: J. Med. Chem. 51 , 7053-6, (2008)

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Abstract

The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze the physiological roles of these enzymes in epigenetic signaling.