STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells.
Zhou L, Kawate T, Liu X, Kim YB, Zhao Y, Feng G, Banerji J, Nash H, Whitehurst C, Jindal S, Siddiqui A, Seed B, Wolfe JL.
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.