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Purity: ≥98%
| Targets |
Tegatrabetan targets β-catenin, a key transcriptional coactivator in the Wnt signaling pathway. It disrupts the binding of β-catenin with the scaffold protein transducin β-like 1 (TBL1). By inhibiting this interaction, tegatrabetan attenuates β-catenin levels in both the cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF complex and the expression of its target genes.
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| ln Vitro |
Tegatrabetan (BC2059; 20-100 nM; 48 hours) promotes dose-dependent apoptosis in cultured human acute myeloid leukemia (AML) HL-60, OCI-AML3, and MV4-11 cells and suppresses cell proliferation in suspension culture for more than 120 hours [1]. Tegatrabetan (20 and 50 nM; 24 hours) causes the cell cycle's G2/M phase to diminish concurrently with a minor but considerable accumulation of cells in the G0/G1 phase [1]. In OCI-AML3, HL-60, and MV4-11 cells, tegatrabetan (100 nM, 24 hours) reduces β-catenin levels and its target genes, such as c-MYC and survivin, without changing TBL1 levels [1].
In vitro, tegatrabetan reduces Wnt3a-induced transcriptional activity in STF3a cells, which exhibit constitutive Wnt activation, when used at a concentration of 1 µM. It attenuates β-catenin levels in both the cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF complex and the expression of its target gene axin 2. The compound's activity is assessed using Wnt reporter assays. |
| ln Vivo |
The median survival of mice treated intravenously with tatetrabetan (BC2059; 1.0 or 5.0 mg/kg/day) increased dramatically from about 17.5 days to 39 days. Intravenous Tegatrabetan (10 mg/kg/day) treatment was the only way to increase median survival to 51.5 days [1].
In vivo, tegatrabetan is orally bioavailable and has potential anticancer activity. As a β-catenin antagonist, it inhibits Wnt/β-catenin signaling, which is frequently dysregulated in various cancers. The compound has been studied in preclinical models of cancer, demonstrating antitumor activity by disrupting β-catenin-mediated transcription. Its oral bioavailability makes it suitable for oral administration in therapeutic settings. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for tegatrabetan measure its disruption of β-catenin-TBL1 binding. The interaction between β-catenin and TBL1 is assessed using co-immunoprecipitation or pull-down assays in the presence of varying concentrations of the compound. The compound's ability to inhibit this protein-protein interaction is quantified. Wnt/β-catenin signaling activity is assessed using reporter gene assays in cells with constitutive Wnt activation.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: HL-60, OCI-AML3 and MV4-11 Cell Tested Concentrations: 20, 50 and 100 nM Incubation Duration: 48 hrs (hours) Experimental Results: Dose-dependent inhibition of cell proliferation. Cell cycle analysis[1] Cell Types: OCI-AML3 Cell Tested Concentrations: 20 and 50 nM Incubation Duration: 24 hrs (hours) Experimental Results: Dose-dependent induction of cell cycle growth arrest. Western Blot Analysis[1] Cell Types: OCI-AML3, HL-60 and MV4-11 Cell Tested Concentrations: 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Treatment diminished β-Catenin expression levels. In vitro cell-based assays for tegatrabetan use cancer cell lines with constitutive Wnt/β-catenin activation. Cells are treated with serial dilutions of the compound, and β-catenin levels are measured by Western blotting. Transcriptional activity of the TCF4/LEF complex is assessed using reporter gene assays. The expression of β-catenin target genes such as axin 2 is measured by qPCR. Cell viability and proliferation are assessed using MTT or colony formation assays. |
| Animal Protocol |
Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse bearing OCI-AML3 xenografts [1]
Doses: 1 mg/kg; 5 mg/kg; 10 mg/kg Route of Administration: intravenous (iv) (iv)injection; 1 mg/kg daily, weekly 4 days, either 5 mg/kg or 10 mg/kg BC2059 twice weekly (Tuesday and Thursday) for 3 weeks. Experimental Results: Treatment Dramatically improved survival of NOD/SCID (severe combined immunodeficient) mouse carrying OCI-AML3 xenografts. In vivo animal models for tegatrabetan include mouse xenograft models of Wnt-driven cancers. The compound is administered orally, and its effects on tumor growth, β-catenin levels, and target gene expression are evaluated. Pharmacodynamic studies measure β-catenin signaling inhibition in tumor tissues. Dose-response studies establish the effective dose for antitumor activity. The compound's oral bioavailability is confirmed in pharmacokinetic studies. |
| ADME/Pharmacokinetics |
Tegatrabetan has a molecular formula of C28H36N4O6S2 and a molecular weight of 588.74. The compound is orally bioavailable and is administered orally in preclinical studies. It is soluble in DMSO and other organic solvents. The compound is stored as a powder at -20°C. Pharmacokinetic parameters including half-life, bioavailability, and tissue distribution are documented in research publications.
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| Toxicity/Toxicokinetics |
Toxicity data for tegatrabetan are available from preclinical safety studies. As a Wnt/β-catenin pathway inhibitor, the compound may affect normal stem cell function and tissue homeostasis. The compound is for research use only and not for human use. Appropriate safety precautions should be taken during handling. The safety margin is determined from toxicology studies.
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| References | |
| Additional Infomation |
Tegavivint is a small-molecule inhibitor of the Wnt/β-catenin signaling pathway with potential antitumor activity. After intravenous injection, tegavivint binds to the transduction protein β-like protein 1 (TBL1), disrupting the binding of β-catenin to TBL1. This promotes β-catenin degradation, reduces β-catenin levels in the nucleus and cytoplasm, and decreases the transcriptional activity of transcription factor 4 (TCF4) and the expression of its target genes, cyclin D1, c-Myc, and survivin. The Wnt/β-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway can lead to tumor cell proliferation. β-catenin is frequently mutated in various tumors.
Tegatrabetan is also known as BC2059, BC-2059, and Tegavivint. It is an orally bioavailable and potent β-catenin inhibitor with potential anticancer activity. The compound disrupts the binding of β-catenin with the scaffold protein transducin β-like 1 (TBL1), attenuating β-catenin levels and reducing the transcriptional activity of the TCF4/LEF complex. It is used for research purposes only and is not approved for clinical use. |
| Molecular Formula |
C28H36N4O6S2
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|---|---|
| Molecular Weight |
588.7386
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| Exact Mass |
588.207
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| CAS # |
1227637-23-1
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| Related CAS # |
1227637-23-1
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| PubChem CID |
46212391
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| Appearance |
White to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
757.6±70.0 °C at 760 mmHg
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| Flash Point |
412.0±35.7 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.687
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| LogP |
4.86
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
40
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@@H]1C[C@@H](CN(C1)S(=O)(=O)C2=CC3=C(C=C2)C(=C4C=CC(=CC4=C3N=O)S(=O)(=O)N5C[C@@H](C[C@@H](C5)C)C)NO)C
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| InChi Key |
OMWCXCBGEFHCTN-FGYAAKKASA-N
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| InChi Code |
InChI=1S/C28H36N4O6S2/c1-17-9-18(2)14-31(13-17)39(35,36)21-5-7-23-25(11-21)28(30-34)26-12-22(6-8-24(26)27(23)29-33)40(37,38)32-15-19(3)10-20(4)16-32/h5-8,11-12,17-20,29,33H,9-10,13-16H2,1-4H3/t17-,18+,19-,20+
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| Chemical Name |
N-[3,6-bis[[(3S,5R)-3,5-dimethylpiperidin-1-yl]sulfonyl]-10-nitrosoanthracen-9-yl]hydroxylamine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~84.93 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.25 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.25 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6985 mL | 8.4927 mL | 16.9854 mL | |
| 5 mM | 0.3397 mL | 1.6985 mL | 3.3971 mL | |
| 10 mM | 0.1699 mL | 0.8493 mL | 1.6985 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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