| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
| Targets |
JW-67 targets the protein-protein interaction between β-catenin and TCF4, a key step in the Wnt/β-catenin signaling pathway. In the presence of Wnt signaling, β-catenin accumulates in the nucleus and binds to TCF/LEF transcription factors, leading to the expression of target genes. By inhibiting this interaction, JW-67 prevents the transcription of these genes, thereby suppressing Wnt-driven cell proliferation and survival.
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|---|---|
| ln Vitro |
JW67 (1 μM; 24 hours) lowers the active form of β-catenin and raises the concentration of AXIN2 [1]. Colon cancer cell line proliferation is inhibited and Wnt target gene expression is impacted by JW67 [1]. With a GI50 value of 7.8 μM, JW67 exhibits a concentration-dependent decrease in proliferation [1].
In vitro, JW-67 is a potent inhibitor of the Wnt/β-catenin pathway. It inhibits the interaction between β-catenin and TCF4, as demonstrated in biochemical assays. In cell-based reporter assays, it inhibits Wnt/β-catenin-mediated transcription with an IC50 in the low micromolar range. It shows selectivity for the Wnt pathway over other signaling pathways. |
| ln Vivo |
In vivo, JW-67 has demonstrated antitumor activity in preclinical models of Wnt-dependent cancers. In mouse xenograft models, administration of JW-67 leads to significant inhibition of tumor growth. This is associated with a reduction in the expression of Wnt target genes in tumor tissue, confirming target engagement.
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| Enzyme Assay |
The activity of JW-67 is assessed using in vitro biochemical assays that measure the interaction between β-catenin and TCF4. Techniques such as TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) or AlphaScreen can be used to quantify the inhibition of the protein-protein interaction in the presence of the compound. Its ability to inhibit Wnt-mediated transcription is confirmed using reporter gene assays.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: SW480 Cell Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Increased AXIN2 expression. RT-PCR[1] Cell Types: SW480 cells Tested Concentrations: 10 or 25μM Incubation Duration: 72 hrs (hours) Experimental Results: diminished in vitro growth of SW480 CRC cells by inhibiting G1/S cell cycle progression. The cellular activity of JW-67 is evaluated in cancer cell lines with active Wnt/β-catenin signaling. Cells are treated with JW-67, and the expression of Wnt target genes, such as AXIN2 and MYC, is measured by qRT-PCR. The effect on cell viability and proliferation is measured using standard assays. |
| Animal Protocol |
In animal studies, JW-67 is typically administered to immunodeficient mice bearing subcutaneous xenografts of Wnt-dependent cancer cell lines. The route of administration and dosing regimen are determined based on its pharmacokinetic properties. Tumor growth inhibition is measured, and tumors are harvested for pharmacodynamic analysis to confirm target gene repression.
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| ADME/Pharmacokinetics |
JW-67 is a small molecule with a molecular weight of approximately 400 g/mol. It is soluble in DMSO and is typically stored as a powder at -20°C. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology data for JW-67 is limited, as it is a research compound. Its safety profile has not been established in formal toxicology studies. Its use is limited to research applications and it is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
JW-67 (CAS: 442644-28-2) is a valuable research tool for studying the Wnt/β-catenin signaling pathway. By inhibiting the β-catenin-TCF4 interaction, it provides a means to investigate the role of Wnt signaling in cancer and other diseases. It is a key compound for validating the Wnt pathway as a therapeutic target and for developing new anti-cancer agents.
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| Molecular Formula |
C21H18N2O6
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|---|---|
| Molecular Weight |
394.377
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| Exact Mass |
394.116
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| CAS # |
442644-28-2
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| PubChem CID |
644733
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.846
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
29
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
BTXRSHKJNDFHGA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18N2O6/c24-17-20(13-5-1-3-7-15(13)22-17)26-9-19(10-27-20)11-28-21(29-12-19)14-6-2-4-8-16(14)23-18(21)25/h1-8H,9-12H2,(H,22,24)(H,23,25)
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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 (~126.78 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.34 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 (6.34 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5356 mL | 12.6781 mL | 25.3563 mL | |
| 5 mM | 0.5071 mL | 2.5356 mL | 5.0713 mL | |
| 10 mM | 0.2536 mL | 1.2678 mL | 2.5356 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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