Novel tertiary sulfonamides as potent anti-cancer agents.

•76,000 compounds were tested for inhibition of a Wnt transcription assay.•One “hit” compound was found to be reproducibly potent at Wnt inhibition.•The “hit” was optimized by medicinal chemistry and “lead” 19 was examined.•Compound 19 potently inhibited human breast cancer cell lines.•19 synergized Doxorubicin to inhibit cancer proliferation in vitro and in vivo.