Abstract
Inhibitors of the MAP kinase p38 provide a novel approach for the treatment of osteoporosis, inflammatory disorders, and cancer. We have identified N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N'-(4-(4-pyridinylmethyl)phenyl)urea as a potent and selective p38 kinase inhibitor in biochemical and cellular assays. This compound is orally active in two acute models of cytokine release (TNF-induced IL-6 and LPS-induced TNF) and a chronic model of arthritis (20-day murine collagen-induced arthritis).
MeSH terms
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Administration, Oral
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Animals
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Arthritis / drug therapy
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Cytokines / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Mice
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Urea / analogs & derivatives
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Urea / chemical synthesis*
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Urea / chemistry
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Urea / pharmacology*
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Urea / therapeutic use
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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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N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N'-(4-(4-pyridinylmethyl)phenyl)urea
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Urea
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases