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

Laura Di Magno, Fiorella Di Pastena, Michela Puxeddu, Giuseppe La Regina, Antonio Coluccia, Alessia Ciogli, Simone Manetto,Marella Maroder, Gianluca Canettieri, Romano Silvestri, Marianna Nalli. ChemMedChem 202015, 2264-2268.

The Wnt/b-catenin pathway is often found deregulated in cancer. The aberrant accumulation of b-catenin in the cell nucleus results in the development of various malignancies. Specific drugs against this signaling pathway for clinical treatments have not been approved yet. Here we report inhibitors of b-catenin signaling of potential therapeutic value as anticancer agents. Compound 14 inhibits the effect on Wnt reporter with IC50 of 7.0 μM, significantly reduces c-MYC levels, inhibits HCT116 colon cancer cell growth with IC50 of 20.2 mM, does not violate the Lipinski and Veber rules and shows predicted Caco-2 and MDCK cell permeability Papp >500 nm/s. Compound 14 seems to have potential for the development of new anticancer therapies