biostudies-literatureNalli MAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteUniversità Cattolica del Sacro CuoreChina Academy of Traditional Chinese MedicineSapienza Università di RomaFondazione Umberto VeronesiInstitut Pasteur Italy1087-1103https://www.ebi.ac.uk/biostudies/studies/S-EPMC10353061biostudies-literatureUnknown6(7)Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel <i>N</i>-(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds <b>5</b>-<b>10</b> showed strong inhibition of the luciferase activity. Compounds <b>5</b> and <b>6</b> inhibited the MDA-MB-231, HCC1806, and HCC1937 TNBC cells. Compound <b>9</b> induced in vitro cell death in SW480 and HCT116 cells and in vivo tumorigenicity of a human colorectal cancer line HCT116. In a co-immunoprecipitation study in HCT116 cells transfected with Myc-tagged T-cell factor 4 (Tcf-4), compound <b>9</b> abrogated the association between β-catenin and Tcf-4. The crystallographic analysis of the β-catenin Armadillo repeats domainACS pharmacology & translational scienceNovel <i>N</i>-(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.PMC10353061RM120172A7EAD07CIG 2020 24703IG 2021 25833RG120172AD61BE52MFGA 21899RM11916B5598E3C4RG12117A61923A6FA1-U21-205-01010202RG11816428A9B4D5RM12117A85D9076BWen YSebastiani JMasci DLa Regina GSette CCapelli DD'Angelo SStornaiuolo MLiu TD'Ambrosio MLiu XDi Pastena FBiagioni SPuxeddu MRipa SNaro CUrbani AColuccia AParisi ADondio GSorato ACanettieri GNalli MPastore ABigogno CSilvestri RMontanari RDi Magno LOrlando VfalseNovel <i>N</i>-(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel <i>N</i>-(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds <b>5</b>-<b>10</b> showed strong inhibition of the luciferase activity. Compounds <b>5</b> and <b>6</b> inhibited the MDA-MB-231, HCC1806, and HCC1937 TNBC cells. Compound <b>9</b> induced in vitro cell death in SW480 and HCT116 cells and in vivo tumorigenicity of a human colorectal cancer line HCT116. In a co-immunoprecipitation study in HCT116 cells transfected with Myc-tagged T-cell factor 4 (Tcf-4), compound <b>9</b> abrogated the association between β-catenin and Tcf-4. The crystallographic analysis of the β-catenin Armadillo repeats domain2023-01-01T00:00:00Z2023 Jul2026-06-02T04:36:49.065Z2024-10-16T07:23:54.639ZS-EPMC103530613747001810.1021/acsptsci.3c00092