Abstract
A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-microM IC(50) values, and suppresses LPS-induced TNFalpha levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Aminoquinolines / chemical synthesis
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Aminoquinolines / chemistry*
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Aminoquinolines / pharmacology
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Aniline Compounds / chemical synthesis
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Aniline Compounds / chemistry*
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Aniline Compounds / pharmacology
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Cell Line
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High-Throughput Screening Assays
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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 / metabolism
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Kinetics
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Lipopolysaccharides / pharmacology
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Aminoquinolines
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Aniline Compounds
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Intracellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Protein Kinase Inhibitors
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Quinolines
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Tumor Necrosis Factor-alpha
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quinoline
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases