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.
Li Zhou  1 ,  Tomohiko Kawate ,  Xiaorong Liu ,  Young Bae Kim ,  Yajuan Zhao ,  Guohong Feng ,  Julian Banerji ,  Huw Nash ,  Charles Whitehurst ,  Satish Jindal ,  Arshad Siddiqui ,  Brian Seed ,  Jia L Wolfe
Affiliations
  • 1. Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA.
PMID: 22217933 DOI: 10.1016/j.bmc.2011.12.006
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.

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