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.

Our Publications

Tegavivint (BC2059) has been extensively studied in several in vitro and in vivo models with therapeutic potential in a broad range of tumors. Peer-reviewed published research articles summarizing tegavivint’s binding affinity, potency, selectivity, pharmacodynamics, and anti-tumor activity in vitro and in vivo can be found below.

  1. Soldi R. et al. J Med. Chem 2015 PMID: 26182238
  2. Savvidou I et al. Mol Cancer Ther 2017 PMID: 28500235
  3. Nomura M et al. JNCI 2019 PMID: 30793158 
  4. Saenz DT et al. Leukemia 2019 PMID: 30575820
  5. Lee D.J Clin Oncol 2022 doi: 10.1200/JCO.2022.40.16_suppl.11523
  6. Fiskus W et al. Leukemia 2014 PMID: 25482131
  7. Nomura M et al. JNCI 2019 PMID: 30793158
  8. Li J et al. Nature 2008 PMID: 18193033
  9. Dimitrova YN et al. J Biol Chem 2010 PMID: 20181957
  10. Penny MK et al. Cancers (Basel) 2023 PMID: 37509222
Scroll to Top