Activity Analysis of the P2X Receptor Antagonist PPADS against Signal Transducer and Activator of Transcription Proteins

The P2X receptor antagonist PPADS possesses activity against members of the signal transducer and activator of transcription (STAT) family of transcription factors, in particular STAT4, STAT5a, and STAT5b. PPADS protects STAT4 and STAT5a/STAT5b from thermal degradation in cell lysates to a higher extent than STAT3. The data suggest that aromatic disulfonate antagonists of P2X receptors may represent promising starting points for the development of inhibitors of STAT proteins.

The small molecule PPADS is a P2X receptor antagonist. Analysis of a library of known bioactive compounds in competitive fluorescence polarization-based assays indicates that PPADS and its isomer iso-PPADS also possess activity against members of the signal transducer and activator of transcription (STAT) family of transcription factors, in particular STAT4, STAT5a, and STAT5b. These results are also supported by HTRF assays. PPADS protects STAT4 and STAT5a/STAT5b from thermal degradation in cell lysates to a higher extent than STAT3. Combined data from this article and a previous article suggest that aromatic disulfonate antagonists of P2X receptors might serve as promising starting points for the development of inhibitors of STAT proteins.

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