| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
The primary target of JW74 is tankyrase (TNKS1/2), a member of the PARP family that plays a critical role in the Wnt/β-catenin signaling pathway. Tankyrase regulates the stability of AXIN, a scaffold protein that facilitates the phosphorylation and degradation of β-catenin. By inhibiting tankyrase, JW74 induces stabilization of AXIN2, which enhances the formation of the β-catenin destruction complex and promotes the degradation of β-catenin. This leads to reduced nuclear β-catenin levels and inhibition of Wnt target gene transcription. JW74 also inhibits TNKS1/2 through the catalytic PARP domain.
|
|---|---|
| ln Vitro |
In the ST-Luc experiment, JW74 exhibits decreased canonical Wnt signaling, with an IC50 of 790 nM [1]. The MTS assay was used to examine how tankyrase inhibition affected the viability of the cells. Compared to cells treated with DMSO, the viability of U2OS cells treated with 10 μM JW74 for 72 hours was reduced to 80%. After treating U2OS with DMSO or 10 uM JW74 for 48 hours, the expression marker Ki-67 was also measured using flow cytometry. In cells treated with DMSO, Ki-67 expression was 97.5%; in cells treated with JW74, it was 86.7% [2].
In vitro, JW74 is a tankyrase-specific inhibitor that affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. It induces stabilization of AXIN2, resulting in reduced levels of nuclear β-catenin. The compound inhibits the canonical Wnt signaling pathway with an IC₅₀ of 790 nM in the ST-Luc assay. It increases AXIN2 and decreases active β-catenin levels in colorectal cancer cells. JW74 also inhibits TNKS1/2 through the catalytic PARP domain. |
| ln Vivo |
The in vivo effectiveness of JW74 was investigated using SW480 cell xenografts. Relatively higher doses of JW74 (150 or 300 mg/kg) were utilized because the chemical demonstrates strong biological activity as indicated by human liver microsomal study (t1/2=2.5 min) and pharmacokinetic analysis (after each oral injection). Rapidly degraded in the body. ( t1/2=30 minutes, intravenous injection: t1/2=15 minutes). Identification of the presence of JW74 in tumors and plasma by mass spectrometry. JW74 concentrations in tumors ranged from 4.2 to 72.1 μmol/kg for JW74 150 mg/kg, 1.9 to 11.1 μmol/kg for JW74 300 mg/kg, and JW74 concentrations in plasma were 2.8 μM at both dosages [1].
In vivo, JW74 inhibits the growth of tumor cells in both mouse xenograft models of colorectal cancer and in ApcMin mice. By targeting tankyrase and inhibiting Wnt/β-catenin signaling, the compound suppresses tumor growth and promotes apoptosis. The compound's efficacy in ApcMin mice, a model of familial adenomatous polyposis, demonstrates its potential for treating Wnt-driven cancers. However, specific in vivo dosing and administration details are not provided in the available sources. |
| Enzyme Assay |
For tankyrase inhibitors, standard cell-free assays involve measuring the PARP (poly ADP-ribose polymerase) activity of recombinant tankyrase 1/2. The compound is incubated with the enzyme and NAD⁺, and PARylation activity is measured by incorporation of biotin-NAD⁺ or by ELISA to determine IC₅₀ values.
|
| Cell Assay |
For Wnt/β-catenin inhibitors, standard cellular assays use cells with a Wnt-responsive luciferase reporter (ST-Luc assay). Cells are treated with the test compound, and luciferase activity is measured to determine IC₅₀ values. AXIN2 and β-catenin levels are measured by western blot. Cell proliferation, apoptosis, and differentiation are assessed in cancer cell lines.
|
| Animal Protocol |
For in vivo evaluation of Wnt/β-catenin inhibitors, standard animal models include mouse xenograft models of colorectal cancer and ApcMin mice, a genetic model of intestinal tumorigenesis. The compound is typically administered orally or intraperitoneally for 2-4 weeks. Tumor growth, AXIN2 and β-catenin levels, apoptosis markers, and survival are assessed.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for JW74 is not extensively provided in the available sources. The compound has a molecular weight of 456.52 and formula C₂₄H₂₀N₆O₂S. It is soluble in DMSO at ≥50 mg/mL. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. Comprehensive PK studies would be required for therapeutic development.
|
| Toxicity/Toxicokinetics |
Detailed toxicology data for JW74 is not provided in the available sources. As a research compound targeting Wnt/β-catenin signaling, standard preclinical toxicology would be required for therapeutic development. The compound's effects on normal Wnt signaling in various tissues would need to be evaluated. The compound is for research use only and not for therapeutic applications.
|
| References |
|
| Additional Infomation |
JW74 is a tankyrase-specific inhibitor that inhibits canonical Wnt signaling with an IC₅₀ of 790 nM in the ST-Luc assay. It induces stabilization of AXIN2, resulting in reduced levels of nuclear β-catenin. The compound inhibits tumor growth in mouse xenograft models of colorectal cancer and in ApcMin mice. It has the molecular formula C₂₄H₂₀N₆O₂S and a molecular weight of 456.52. No regulatory approval has been identified.
|
| Molecular Formula |
C24H20N6O2S
|
|---|---|
| Molecular Weight |
456.5196
|
| Exact Mass |
456.136
|
| CAS # |
863405-60-1
|
| PubChem CID |
16013152
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
699.4±65.0 °C at 760 mmHg
|
| Flash Point |
376.8±34.3 °C
|
| Vapour Pressure |
0.0±2.2 mmHg at 25°C
|
| Index of Refraction |
1.700
|
| LogP |
6.37
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
33
|
| Complexity |
596
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC=C(C=C1)C2=NOC(=N2)CSC3=NN=C(N3C4=CC=C(C=C4)OC)C5=CC=NC=C5
|
| InChi Key |
KRIKILRRJCIWNB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H20N6O2S/c1-16-3-5-17(6-4-16)22-26-21(32-29-22)15-33-24-28-27-23(18-11-13-25-14-12-18)30(24)19-7-9-20(31-2)10-8-19/h3-14H,15H2,1-2H3
|
| Chemical Name |
5-[[4-(4-methoxyphenyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]sulfanylmethyl]-3-(4-methylphenyl)-1,2,4-oxadiazole
|
| Synonyms |
JW 74; JW-74; JW74
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~109.52 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 27.5 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: ≥ 2.75 mg/mL (6.02 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 27.5 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 | 2.1905 mL | 10.9524 mL | 21.9048 mL | |
| 5 mM | 0.4381 mL | 2.1905 mL | 4.3810 mL | |
| 10 mM | 0.2190 mL | 1.0952 mL | 2.1905 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
