STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells

Bioorg Med Chem. 2012 Jan 15;20(2):750-8. doi: 10.1016/j.bmc.2011.12.006. Epub 2011 Dec 17.

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.

MeSH terms

  • Cell Line
  • Chemokine CCL26
  • Chemokines, CC / metabolism*
  • Dimerization
  • Epithelial Cells / metabolism*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Interleukin-4 / pharmacology
  • Phosphorylation
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Receptors, Interleukin-4 / metabolism
  • STAT6 Transcription Factor / antagonists & inhibitors*
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Stereoisomerism

Substances

  • CCL26 protein, human
  • Chemokine CCL26
  • Chemokines, CC
  • Indoles
  • Pyridines
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • Interleukin-4