Abstract
A novel series of inhibitors for mitogen activated protein kinase-activated protein kinase 2 (MK-2) are reported. These squarate based inhibitors were identified via a high-throughput screen. An MK2 co-structure with the starting ligand was obtained and a structure based approach was followed to optimize potency and selectivity.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cyclobutanes / chemistry*
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Cyclobutanes / pharmacology*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Models, Molecular
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Monocytes / cytology
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein Transport
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Cyclobutanes
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Protein Kinase Inhibitors
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Tumor Necrosis Factor-alpha
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Mitogen-Activated Protein Kinase 1
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squaric acid