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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology*
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Humans
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Ketoglutaric Acids / chemical synthesis
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Ketoglutaric Acids / chemistry
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Ketoglutaric Acids / pharmacology*
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Models, Molecular
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Molecular Structure
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Oxidoreductases, N-Demethylating / antagonists & inhibitors*
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Oxidoreductases, N-Demethylating / metabolism
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Protein Structure, Tertiary
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Ketoglutaric Acids
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Oxidoreductases, N-Demethylating