| Targets |
xStAx-VHLL TFA targets β-catenin, a key transcriptional coactivator in the Wnt signaling pathway. β-catenin is essential for embryonic development and tissue homeostasis, but its dysregulation is implicated in various cancers. The compound operates through a PROTAC mechanism: it binds to β-catenin via the xStAx moiety and recruits the E3 ubiquitin ligase via the VHL ligand, leading to ubiquitination and subsequent proteasomal degradation of β-catenin.
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| ln Vitro |
In vitro, xStAx-VHLL TFA promotes β-catenin ubiquitination and sustains its degradation. This results in strong inhibition of Wnt signaling. In cancer cells, degradation of β-catenin suppresses Wnt-driven transcription of target genes involved in cell proliferation and survival, leading to anti-cancer activity. The compound's potency and efficacy are determined by measuring β-catenin protein levels (by Western blotting) and Wnt signaling activity (by luciferase reporter assays).
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| ln Vivo |
In vivo, xStAx-VHLL TFA has demonstrated anti-cancer activity in preclinical models. By degrading β-catenin and inhibiting Wnt signaling, the compound suppresses tumor growth in Wnt-driven cancers. The PROTAC mechanism provides a catalytic and sustained degradation of the target protein. Detailed in vivo efficacy data, including effects on tumor growth in xenograft models, are described in the primary literature.
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| Enzyme Assay |
Non-cellular binding assays for xStAx-VHLL TFA involve studying its interactions with β-catenin and the VHL E3 ubiquitin ligase. Binding affinity to β-catenin can be measured using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The formation of the ternary complex (PROTAC-β-catenin-VHL) can be assessed using biochemical assays such as AlphaScreen or pull-down experiments.
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| Cell Assay |
In vitro cellular experiments with xStAx-VHLL TFA are conducted in cancer cell lines with activated Wnt signaling. Cells are treated with the compound at various concentrations, and β-catenin protein levels are assessed by Western blotting to confirm degradation. Wnt signaling activity is measured using luciferase reporter assays containing TCF/LEF response elements. Cell viability and proliferation are evaluated using standard assays such as CellTiter-Glo or MTT. Apoptosis induction is assessed by caspase activity measurements.
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| Animal Protocol |
In vivo animal studies for xStAx-VHLL TFA are performed in murine xenograft models using cancer cell lines with activated Wnt signaling. Tumor-bearing mice are treated with the compound via appropriate routes of administration. Tumor growth is monitored over time, and endpoints include tumor volume measurements, survival analysis, and pharmacodynamic assessments of β-catenin degradation and Wnt signaling inhibition in tumor tissues. Efficacy is compared to vehicle controls.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of xStAx-VHLL TFA are characterized during preclinical development. As a PROTAC molecule, it has a larger molecular weight and different physicochemical properties compared to traditional small molecule inhibitors. The TFA salt form enhances solubility. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution would be determined in appropriate animal models. Storage conditions should follow the supplier's recommendations.
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| Toxicity/Toxicokinetics |
Toxicity data for xStAx-VHLL TFA are generated during preclinical development. As a β-catenin degrader and Wnt signaling inhibitor, potential toxicities may include effects on normal tissues where Wnt signaling is essential for homeostasis. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions for research use only.
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| References | |
| Additional Infomation |
xStAx-VHLL TFA is a PROTAC that degrades β-catenin and inhibits Wnt signaling. It is formed by coupling xStAx to a VHL ligand. The compound promotes β-catenin ubiquitination. It has anti-cancer activity and can be used in cancer research. All products are for research use only and not for human therapeutic applications.
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| Molecular Formula |
C154H244N48O29.XC2HF3O2
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| Molecular Weight |
3231.89 (free base)
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| Appearance |
White to off-white solid powder
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O :~100 mg/mL (~with sonication)
DMSO :~100 mg/mL (with sonication) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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.
Products are for research use only; We do not sell to patients
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