Abstract
Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Line
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Chromosomes, Human, Pair 6
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Cloning, Molecular
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Cytokines / antagonists & inhibitors
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Cytokines / biosynthesis*
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DNA, Complementary
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Humans
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Imidazoles / pharmacology
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Inflammation Mediators*
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Interleukin-1 / biosynthesis
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Monocytes / drug effects
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Monocytes / metabolism
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Peptide Fragments
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Pyridines / pharmacology
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Radioligand Assay
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
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p38 Mitogen-Activated Protein Kinases
Substances
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Cytokines
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DNA, Complementary
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Imidazoles
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Inflammation Mediators
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Interleukin-1
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Peptide Fragments
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Pyridines
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Recombinant Proteins
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SB 206718
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Tumor Necrosis Factor-alpha
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
Associated data
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GENBANK/L35263
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GENBANK/L35264