Abstract
A benzopyranopyridine inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2) is prepared rapidly and efficiently in one step using microwave dielectric heating, whereas a substrate-selective p38 MAPK inhibitor was prepared using conventional heating techniques. The former had MK2 inhibitory activity above 2.5 microM concentration, whereas the latter showed no MK2 inhibition at 10 microM. However, rather than rescuing the reduced cellular growth rate and aged morphology of hTERT-immortalised WS dermal fibroblasts, both induce a state resembling stress-induced cellular senescence, suggesting that these inhibitors may have limited therapeutic use.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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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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Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 14 / metabolism*
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Molecular Structure
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Phosphorylation / drug effects
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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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Substrate Specificity
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Werner Syndrome / enzymology*
Substances
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Intracellular Signaling Peptides and Proteins
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Protein Kinase Inhibitors
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase 14