Sulfonamide inhibitors of beta-catenin signaling as anticancer agents with different output on c-Myc

1The Wnt/beta-catenin pathway is often found deregulated incancer. The aberrant accumulation of beta-catenin in the cellnucleus results in the development of various malignancies. Specific drugs against this signaling pathway for clinical treat-ments have not been approved yet. Herein we report inhibitorsof beta-catenin signaling of potential therapeutic value asanticancer agents. Ethyl 4-((4-(trifluoromethyl)phenyl)sulfonamido)benzoate (compound 14) inhibits the effect onWnt reporter with an IC50value of 7.0 microM, significantly reducesc-MYC levels, inhibits HCT116 colon cancer cell growth (IC5020.2 microM), does not violate Lipinski and Veber rules, and showspredicted Caco-2 and MDCK cell permeability Papp>500 nm s-1.Compound 14 seems to have potential for the development ofnew anticancer therapies.