Tegatrabetan(also known as Tegavivint; BC-2059; BC 2059; BC2059) is an orally bioavailable and potent β-catenin inhibitor with potential anticancer activity. BC2059 potently induces apoptosis as a single agent and in combination with bortezomib in multiple myeloma. BC2059 induced apoptosis in 10/10 genetically heterogeneous human myeloma cell lines (HMCL) treated with dosages ranging from 50-500nM.

Physicochemical Properties

Molecular Formula	C28H36N4O6S2
Molecular Weight	588.7386
Exact Mass	588.207
CAS #	1227637-23-1
Related CAS #	1227637-23-1
PubChem CID	46212391
Appearance	White to light yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	757.6±70.0 °C at 760 mmHg
Flash Point	412.0±35.7 °C
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.687
LogP	4.86
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	40
Complexity	1020
Defined Atom Stereocenter Count	4
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
InChi Key	OMWCXCBGEFHCTN-FGYAAKKASA-N
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+
Chemical Name	N-[3,6-bis[[(3S,5R)-3,5-dimethylpiperidin-1-yl]sulfonyl]-10-nitrosoanthracen-9-yl]hydroxylamine
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
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.
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.
References	[1]. Pre-clinical efficacy of combined therapy with novel β-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells. Leukemia. 2015 Jun;29(6):1267-78.
Additional Infomation	Tegavivint is a small molecule inhibitor of the Wnt/beta-catenin pathway with potential antineoplastic activity. Upon intravenous administration, tegavivint binds to transducin beta-like protein 1 (TBL1) and disrupts the binding of beta-catenin to TBL1. This promotes beta-catenin degradation, attenuates nuclear and cytoplasmic levels of beta-catenin, and reduces transcriptional activity of transcription factor 4 (TCF4) and expression of its target genes, cyclin D1, c-Myc and survivin. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation. Beta-catenin is frequently mutated in various tumors.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~84.93 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.