Tegatrabetan

SKU: orb1226740

Description

Tegatrabetan (BC-2059, BC2059, Tegavivint) is an orally bioavailable β-catenin antagonist that disrupts the binding of β-catenin to TBL1 and promotes β-catenin degradation, attenuates nuclear and cytoplasmic levels of β-catenin; reduces transcriptional activity of TCF4 and expression of its target genes, cyclin D1, c-MYC and survivin. BC treatment dose-dependently induced apoptosis of cultured and primary AML BPCs; significantly improves the median survival of immune-depleted mice engrafted with either cultured or primary AML BPCs.Blood Cancer Phase 1 Clinical(In Vitro):Tegatrabetan (BC2059; 20-100 nM; 48 hours) inhibits cell proliferation in suspension culture over 120 hours and induces apoptosis of cultured human acute myeloid leukemia (AML) HL-60, OCI-AML3 and MV4-11 cells dose-dependently.Tegatrabetan (20 and 50 nM; 24 hours) induces a modest but significant accumulation of cells in the G0/G1 phase, with a concomitant decline in the G2/M phase of the cell cycle.Tegatrabetan (100 nM, 24 hours) depletes the levels of β-catenin and its target genes, including c-MYC and survivin without affecting the levels of the TBL1 in OCI-AML3, HL-60 and MV4-11 cells.(In Vivo):Tegatrabetan (BC2059; 1.0 or 5.0 mg/kg/day; intravenously) significantly improves the median survival of the mice from approximately 17.5 to 39 days. Treatment with Tegatrabetan (10 mg/kg/day; intravenously) alone further improves the median survival to 51.5 days.

Key Properties

• CAS Number: 1227637-23-1
• MW: 588.74
• Purity: >98% (HPLC)
• Formula: C₂₈H₃₆N₄O₆S₂
• SMILES: O=S(C1=CC2=C(C=C1)/C(C3=CC=C(S(=O)(N4C[C@H](C)C[C@H](C)C4)=O)C=C3/C2=N\O)=N\O)(N5C[C@H](C)C[C@H](C)C5)=O
• Target: Beta-catenin
• Solubility: In Vitro: DMSO : 50 mg/mL (84.93 mM)

Bioactivity

• In Vivo:
  Tegatrabetan (BC2059; 1.0 or 5.0 mg/kg/day; intravenously) significantly improves the median survival of the mice from approximately 17.5 to 39 days. Treatment with Tegatrabetan (10 mg/kg/day; intravenously) alone further improves the median survival to 51.5 days. Animal model: NOD/SCID mice bearing OCI-AML3 xenografts. Dosage: 1 mg/kg; 5 mg/kg; 10 mg/kg. Administration: Intravenously; 1 mg/kg daily 4 days per week or 5 mg/kg or 10 mg/kg of BC2059 twice per week (Tuesday and Thursday) for 3 weeks. Result: Treatment significantly improved survival of NOD/SCID mice bearing OCI-AML3 xenografts.
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• In Vitro:
  Tegatrabetan (BC2059; 20-100 nM; 48 hours) inhibits cell proliferation in suspension culture over 120 hours and induces apoptosis of cultured human acute myeloid leukemia (AML) HL-60, OCI-AML3 and MV4-11 cells dose-dependently. Tegatrabetan (20 and 50 nM; 24 hours) induces a modest but significant accumulation of cells in the G0/G1 phase, with a concomitant decline in the G2/M phase of the cell cycle. Tegatrabetan (100 nM, 24 hours) depletes the levels of β-catenin and its target genes, including c-MYC and survivin without affecting the levels of the TBL1 in OCI-AML3, HL-60 and MV4-11 cells. Cell Proliferation Assay Cell line: HL-60, OCI-AML3 and MV4-11 cells. Concentration: 20, 50, and 100 nM. Incubation time: 48 hours. Result: Dose-dependently inhibited cell proliferation. Cell Cycle Analysis Cell line: OCI-AML3 cells. Concentration: 20 and 50 nM. Incubation time: 24 hours. Result: Dose-dependently induced cell cycle growth arrest. Western blot analysis. Cell line: OCI-AML3, HL-60 and MV4-11 cells. Concentration: 100 nM. Incubation time: 24 hours. Result: Treatment depleted β-Catenin expression levels.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BC-2059 | BC2059 | Tegavivint

Quick Database Links

Gene Symbol

Beta-catenin