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

Journal article

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.

Authors: Rose, N; Ng, S; Mecinović, J; Liénard, B; Bello, S

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 51
• Issue: 22
• Pages: 7053-7056
• Publication date: 2008-11-01
• DOI: 10.1021/jm800936s
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Enzyme Inhibitors; Ketoglutaric Acids; Molecular Structure; Humans; Dose-Response Relationship, Drug; Stereoisomerism; Structure-Activity Relationship; Models, Molecular; Crystallography, X-Ray; Oxidoreductases, N-Demethylating; Protein Structure, Tertiary