Abstract
Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed.
MeSH terms
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Cell Line
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cytokines / biosynthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Imidazoles / chemistry
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Imidazoles / pharmacology*
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Isoenzymes / antagonists & inhibitors
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Models, Molecular
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C-alpha
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Stress, Physiological / metabolism*
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Structure-Activity Relationship
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p38 Mitogen-Activated Protein Kinases
Substances
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Cytokines
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Enzyme Inhibitors
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Imidazoles
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Isoenzymes
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Cyclic AMP-Dependent Protein Kinases
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PRKCA protein, human
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Protein Kinase C
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Protein Kinase C-alpha
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases