Abstract
We have identified two novel MEK5 inhibitors, BIX02188 and BIX02189, which inhibited catalytic function of purified, MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. The compounds also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. These inhibitors offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems.
MeSH terms
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Aniline Compounds / isolation & purification
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Aniline Compounds / pharmacology*
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HeLa Cells
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Humans
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Indoles / isolation & purification
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Indoles / pharmacology*
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MADS Domain Proteins / antagonists & inhibitors
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MADS Domain Proteins / genetics
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MAP Kinase Kinase 5 / antagonists & inhibitors*
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MAP Kinase Kinase 5 / metabolism
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MEF2 Transcription Factors
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Mitogen-Activated Protein Kinase 7 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 7 / metabolism
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Myogenic Regulatory Factors / antagonists & inhibitors
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Myogenic Regulatory Factors / genetics
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / isolation & purification
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Protein Kinase Inhibitors / pharmacology*
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Sorbitol / pharmacology
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Transcriptional Activation / drug effects
Substances
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Aniline Compounds
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BIX 02188
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BIX 02189
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Indoles
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MADS Domain Proteins
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MEF2 Transcription Factors
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MEF2C protein, human
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Myogenic Regulatory Factors
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Protein Kinase Inhibitors
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Sorbitol
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Mitogen-Activated Protein Kinase 7
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MAP Kinase Kinase 5