Abstract
The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration. (R)-84 appears to prevent STAT6 from assuming the active dimer configuration by directly binding the protein and inhibiting tyrosine phosphorylation.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Cell Line
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Chemokine CCL26
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Chemokines, CC / metabolism*
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Dimerization
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Epithelial Cells / metabolism*
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / pharmacology
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Interleukin-4 / pharmacology
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Phosphorylation
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacology
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Receptors, Interleukin-4 / metabolism
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STAT6 Transcription Factor / antagonists & inhibitors*
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STAT6 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Stereoisomerism
Substances
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CCL26 protein, human
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Chemokine CCL26
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Chemokines, CC
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Indoles
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Pyridines
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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Interleukin-4