Tegatrabetan

SKU: orb1301626

Description

Tegatrabetan (BC2059) is a small molecule Wnt/β-catenin pathway inhibitor investigated for its anticancer properties. It is utilized in oncology research to study aberrant Wnt signaling in various cancer models, demonstrating activity in both in vitro cellular assays and in vivo preclinical studies.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1227637-23-1
• MW: 588.74
• Purity: 99.95% (May vary between batches)
• Formula: C₂₈H₃₆N₄O₆S₂
• SMILES: C[C@H]1C[C@@H](C)CN(C1)S(=O)(=O)c1ccc2C(=NO)c3ccc(cc3C(=NO)c2c1)S(=O)(=O)N1C[C@@H](C)C[C@@H](C)C1
• Target: Wnt/beta-catenin
• Solubility: DMSO:60 mg/mL (101.91 mM);10% DMSO+90% Corn Oil:2.5 mg/mL (4.25 mM)

Bioactivity

• In Vivo:
  BC2059 synergizes with the proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor growth and prolongs survival with minor on-target side effects. Collectively, these results demonstrate the efficacy of targeting the Wnt/β-catenin pathway with BC2059 both in vitro and in vivo, at clinically achievable doses.
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• In Vitro:
  BC2059 induces apoptosis in primary multiple myeloma samples in vitro, causing minimal apoptosis on healthy peripheral blood mononuclear cells.
• Cell Research:
  For β-catenin knockdown, 2 mL of 2 × 10^5/mL KMS18 cells were plated into a 12-well plate at day 0 (KMS18 doubling time: 36 hours). At day 1, media were replaced by 1 mL of Opti-MEM , and transfection was carried out with Lipofectamine RNAiMAX . For β-catenin knockdown, we used SignalSilence β-catenin siRNA I and β-catenin siRNA II (Cell Signaling Technology) at concentrations recommended by the manufacturer, whereas Silencer Negative Control No. 1 siRNA was used as a negative control, at the same concentration. Six hours after the transfection, 1 mL of fresh media (RPMI-10% FCS) was added in every well. At days 2 and 3, cells were treated with BC2059 (50, 100, 150 nmol/L) and then harvested at day 4 (72 hours after transfection). Cell death was monitored by PI staining with FACS, whereas untreated cells were collected for β-catenin protein level measurement by immunoblotting. Cells were lysed with RIPA lysis buffer, and 70 μg of protein was separated by 6% SDS-PAGE and blotted onto PVDF as already described. β-Actin (mouse mAb HRP conjugate; Cell Signaling Technology) was used as a loading control.
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• Animal Research:
  Adult age-matched Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were injected (intravenously) with 1 × 10^6 U266 HMCL, carrying the FUL2-TGvector . At day 21, a limited course of treatment was commenced after confirmation of established measurable disease by bioluminescence. Control mice (n = 4) received 17% Solutol HS 15 whereas treated mice received 5 (n = 4) or 10 mg/kg BC2059 (n = 5) twice a week intravenously for 3 consecutive weeks (6 doses in total). Tumor burden was monitored on a weekly basis by in vivo imaging, from the second week of the experiment (day 18) until the first mice reached scientific endpoints. Briefly, mice were anaesthetized, injected intraperitoneally with 125 mg/kg luciferin, and imaged with the Lumina III XR system. Acquisition and analysis were performed with the Living Image system. Peripheral blood counts were evaluated sequentially during the course of the experiment .Upon reaching scientific endpoints (hind limp paralysis, >20% weight loss), mice were humanely euthanized and tissues (skin and colon) were collected. Tissues were formalin fixed and embedded in paraffin, sectioned, and stained with H&E and β-catenin antibody. Images were taken with an Olympus BX51 microscope.
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Storage & Handling

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

Alternative Names

Inhibitor, inhibit, bcatenin, BC 2059, BC2059, BC-2059, betacatenin, beta-catenin, Beta catenin, Wnt/β-catenin, Wnt/betacatenin, Wnt/b-catenin, Wnt, Tegatrabetan, βcatenin, β-catenin

Compound Identifiers

PubChem CID

46212391