Abstract
We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the most promising one in the series.
Keywords:
BIRB-796; P38 MAPK; SPR; TNF-α.
MeSH terms
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Cell Line, Tumor
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / metabolism
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Ligands
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Lipopolysaccharides / chemistry
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Neoplasms / drug therapy
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Neoplasms / enzymology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / chemistry
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Urea / administration & dosage*
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Urea / analogs & derivatives
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Urea / chemistry
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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p38 Mitogen-Activated Protein Kinases / chemistry
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Ligands
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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Urea
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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p38 Mitogen-Activated Protein Kinases