Tegavivint | ß-Catenin pathway inhibitor

Tegavivint chemical structure

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Tegavivint (1227637-23-1) is a potent inhibitor (IC50 = <10 nM) of the ß-catenin pathway.1 Active in vitro in multiple cancer cells with nanomolar potency. Tegavivint displayed efficacy in mouse models of acute myeloid leukemia2, multiple myeloma3, and mantle cell lymphoma4. It inhibits the ß-catenin pathway in a unique way by selectively binding to Transducin Beta-like related protein 1 (TBLR1) leading to displacement of ß-catenin from the TBL1/ß-catenin complex.5 This interaction does not effect Notch, Sonic Hedgehog, or Hippo signaling pathways. Tegavivint promotes a lipid-dependent nonapoptotic cell death that is dependent on the enzyme trans-2,3-enoyl-CoA reductase (TECR).6

References/Citations:

  1. Soldi et al. (2015), Design, Synthesis and Biological Evaluation of a Series of anthracene-9,10-dione dioxime ß-catenin Pathway Inhibitors; J. Med. Chem. 58 5854
  2. Fiskus et al. (2015), Pre-clinical efficacy of combined therapy with novel ß-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells; Leukemia 29 1267
  3. Savvidou et al. (2017), beta-Catenin Inhibitor BC2059 is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma; Mol. Cancer Ther. 16 1765
  4. Pray et al. (2025), Targeting the DNA damage response through TBL1X in mantle cell lymphoma; Blood Adv. 27 2006
  5. Soldi et al. (2021), The Small Molecule BC-2059 Inhibits Wingless/Integrated (Wnt)-Dependent Gene Transcription in Cancer through Disruption of the Transducin ß-Like 1-ß-Catenin Protein Complex; J. Pharmacol. Exp. Ther. 378 77
  6. Leak et al. (2025), Tegavivint triggers TECR-dependent nonapoptotic cancer cell death; Nat. Chem. Biol. 21 1873
1227637-23-1, BC-2059, BC2059, ß-catenin pathway inhibitor, TBLR1, tegatrabetan, tegavivint, Tegavivint supplier
Alternate Name:
Tegatrabetan; BC2059

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Tegavivint (1227637-23-1) is a potent inhibitor (IC50 = <10 nM) of the ß-catenin pathway.1 Active in vitro in multiple cancer cells with nanomolar potency. Tegavivint displayed efficacy in mouse models of acute myeloid leukemia2, multiple myeloma3, and mantle cell lymphoma4. It inhibits the ß-catenin pathway in a unique way by selectively binding to Transducin Beta-like related protein 1 (TBLR1) leading to displacement of ß-catenin from the TBL1/ß-catenin complex.5 This interaction does not effect Notch, Sonic Hedgehog, or Hippo signaling pathways. Tegavivint promotes a lipid-dependent nonapoptotic cell death that is dependent on the enzyme trans-2,3-enoyl-CoA reductase (TECR).6

References/Citations:

  1. Soldi et al. (2015), Design, Synthesis and Biological Evaluation of a Series of anthracene-9,10-dione dioxime ß-catenin Pathway Inhibitors; J. Med. Chem. 58 5854
  2. Fiskus et al. (2015), Pre-clinical efficacy of combined therapy with novel ß-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells; Leukemia 29 1267
  3. Savvidou et al. (2017), beta-Catenin Inhibitor BC2059 is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma; Mol. Cancer Ther. 16 1765
  4. Pray et al. (2025), Targeting the DNA damage response through TBL1X in mantle cell lymphoma; Blood Adv. 27 2006
  5. Soldi et al. (2021), The Small Molecule BC-2059 Inhibits Wingless/Integrated (Wnt)-Dependent Gene Transcription in Cancer through Disruption of the Transducin ß-Like 1-ß-Catenin Protein Complex; J. Pharmacol. Exp. Ther. 378 77
  6. Leak et al. (2025), Tegavivint triggers TECR-dependent nonapoptotic cancer cell death; Nat. Chem. Biol. 21 1873