Abstract
Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.
MeSH terms
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Cell Line
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Cell Membrane Permeability
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Histone Demethylases / antagonists & inhibitors*
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Histone Demethylases / chemistry
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Histone Demethylases / metabolism
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Humans
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Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors*
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Jumonji Domain-Containing Histone Demethylases / chemistry
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Jumonji Domain-Containing Histone Demethylases / metabolism
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Models, Molecular
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Molecular Docking Simulation
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Pyrimidinones / chemistry*
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Pyrimidinones / pharmacokinetics
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Pyrimidinones / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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KDM4C protein, human
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Pyrimidinones
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Histone Demethylases
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Jumonji Domain-Containing Histone Demethylases
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KDM4D protein, human
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KDM5C protein, human