| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Target: beta-catenin (CTNNB1, KD = 54.96 nM). beta-catenin-IN-3 binds to an allosteric site on the surface of beta-catenin, distinct from the binding site of TCF/LEF transcription factors. This binding destabilizes beta-catenin or prevents its interaction with TCF/LEF, blocking the transcription of Wnt target genes (c-MYC, cyclin D1, AXIN2, LGR5) and reducing beta-catenin-driven cancer cell proliferation.
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| ln Vitro |
In vitro, beta-catenin-IN-3 binds to beta-catenin with a KD of 54.96 nM measured by surface plasmon resonance. It significantly inhibits the viability of beta-catenin-driven cancer cell lines, including colorectal cancer (HCT116, DLD1) and hepatocellular carcinoma (HCC) cells, with EC50 values in the low micromolar range (1-10 uM). It reduces beta-catenin/TCF transcriptional activity by >50% at concentrations of 5-10 uM.
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| ln Vivo |
No in vivo efficacy data have been published for beta-catenin-IN-3. Based on its potent beta-catenin binding and anti-proliferative activity in vitro, it is expected to suppress tumor growth in xenograft models of colorectal cancer, hepatocellular carcinoma, and other Wnt-driven cancers. The compound is a promising lead for developing beta-catenin-targeted cancer therapies.
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| Enzyme Assay |
For cell-free binding assays (SPR): recombinant beta-catenin protein (50-100 ug) is immobilized on a CM5 sensor chip. Varying concentrations of beta-catenin-IN-3 (0.1-1000 nM) are injected in running buffer (10 mM HEPES, pH 7.4, 150 mM NaCl, 0.05% Tween-20) at a flow rate of 30 uL/min. Association and dissociation phases are monitored. KD (54.96 nM) is calculated using BIAevaluation software. For fluorescence polarization competition assays: labeled beta-catenin inhibitor probe is used to measure displacement.
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| Cell Assay |
For cell-based assays: beta-catenin-driven cancer cell lines (HCT116, DLD1 colorectal; HepG2, Huh7 hepatocellular) are seeded in 96-well plates and treated with beta-catenin-IN-3 (0.1-100 uM, 48-72 h). Cell viability is measured by MTT or CellTiter-Glo assay. beta-catenin/TCF transcriptional activity is measured by TOPFlash/FOPFlash luciferase reporter assays. Cells are co-transfected with Super 8× TOPFlash or FOPFlash reporter plasmids and treated with compound for 24-48 h. Luciferase activity is normalized to Renilla. c-MYC and cyclin D1 expression is measured by qPCR and Western blot.
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| Animal Protocol |
For in vivo animal studies: potential protocol involves xenograft mouse models bearing HCT116 or DLD1 colorectal cancer cells, or HepG2 hepatocellular carcinoma cells. beta-catenin-IN-3 would be administered intraperitoneally or orally (10-50 mg/kg) daily for 2-3 weeks. Tumor volume is measured by calipers. Tumor tissues are harvested for Western blot analysis of c-MYC, cyclin D1, and beta-catenin target genes, and for immunohistochemistry (Ki67, cleaved caspase-3). No published data available.
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| ADME/Pharmacokinetics |
PK properties of beta-catenin-IN-3: For a small molecule beta-catenin inhibitor (MW 484.25, ClogP ∼4.5), predicted PK in rodents after oral administration: moderate oral bioavailability (∼20-40%), Tmax 2-4 h, plasma half-life 4-8 h. Volume of distribution is moderate to large (∼3-5 L/kg), suggesting extensive tissue distribution. Plasma protein binding is high (>90%). Metabolism is likely via CYP450-mediated oxidation. The compound is soluble in DMSO, and in vivo formulation may use DMSO:PEG300:Tween80:Saline (10:40:5:45). No formal PK studies have been published.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for beta-catenin-IN-3. Based on its mechanism, inhibition of beta-catenin in normal tissues may cause adverse effects, including impaired intestinal homeostasis (since Wnt/beta-catenin is essential for intestinal stem cell maintenance), reduced bone formation (via effects on osteoblasts), and potential hair loss (as beta-catenin is required for hair follicle development). No acute toxicity or LD50 studies have been published. The compound is for research use only.
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| References | |
| Additional Infomation |
beta-catenin-IN-3 is a research compound not yet approved for clinical use. It is a valuable chemical probe for studying Wnt/beta-catenin signaling and for validating beta-catenin as a therapeutic target in cancer. It has potential applications in colorectal cancer (where APC mutations cause beta-catenin activation), hepatocellular carcinoma, pancreatic cancer, and other Wnt-driven malignancies. It is a promising lead for developing beta-catenin-targeted therapies that are selective for the allosteric site, potentially overcoming off-target toxicities.
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| Molecular Formula |
C19H20BR2N2OS
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|---|---|
| Molecular Weight |
484.25
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| Exact Mass |
483.964
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| CAS # |
1005288-15-2
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| PubChem CID |
5913409
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| Appearance |
White to off-white solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
584
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C=CC1=CC(Br)=CC(Br)=C1O)C(NC1CC2CC1C1C2CC=C1)=S
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| InChi Key |
VPOJWIBWEJWBKC-SNAWJCMRSA-N
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| InChi Code |
InChI=1S/C19H20Br2N2OS/c20-12-6-10(18(24)16(21)9-12)4-5-22-19(25)23-17-8-11-7-15(17)14-3-1-2-13(11)14/h1,3-6,9,11,13-15,17,24H,2,7-8H2,(H2,22,23,25)/b5-4+
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| Chemical Name |
1-[(E)-2-(3,5-dibromo-2-hydroxyphenyl)ethenyl]-3-(8-tricyclo[5.2.1.02,6]dec-4-enyl)thiourea
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: ~100 mg/mL (~206.5 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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 (5.16 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0650 mL | 10.3252 mL | 20.6505 mL | |
| 5 mM | 0.4130 mL | 2.0650 mL | 4.1301 mL | |
| 10 mM | 0.2065 mL | 1.0325 mL | 2.0650 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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