Our Science

Dysregulated Wnt/beta-catenin signaling is involved within several hallmarks of cancer, making it an attractive therapeutic target in oncology. Unfortunately, key members of this pathway (including beta-catenin) have either been resistant to conventional drug development or plagued with off-target toxicities.  Transducin Beta-like Protein 1 (TBL1) is a newly characterized target in the Wnt/beta-catenin pathway that provides a novel way to inhibit beta-catenin oncogenic activity. TBL1 binds to accumulated nuclear beta-catenin forming an active transcription complex that prevents nuclear degradation of beta-catenin and activates genes necessary for the Wnt/beta-catenin oncogenic activity. Tegavivint is a novel, small-molecule inhibitor that binds to TBL1 and disrupts the interaction between beta-catenin and TBL1, thus promoting the degradation of nuclear beta-catenin and preventing the transcription of Wnt/beta-catenin targeted oncogenes. ^1-4 Preclinical studies have shown tegavivint inhibits beta catenin activity without overt toxicity, and has been shown to not be affected by CTNNB1 gain-of-function mutations typically found in cancer cells.^{2-3, 5-10} In parallel with the tegavivint program, Iterion has ongoing R&D programs investigating and developing 2nd generation TBL1 inhibitors.