| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EC50: 3.8 nM (β-Catenin-SCFβ-TrCP)[1]
NRX-252262 targets the interaction between β-catenin and its E3 ligase SCF^β-TrCP. By enhancing this protein-protein interaction, the compound promotes the ubiquitination and proteasomal degradation of β-catenin, particularly mutant forms that are resistant to normal degradation. This mechanism of action is distinct from traditional Wnt pathway inhibitors that target upstream receptors or downstream transcription factors. NRX-252262 offers a targeted approach to reducing β-catenin levels in cells with aberrant Wnt signaling. |
|---|---|
| ln Vitro |
In cells, NRX-252262 (35 μM) degrades β-catenin in S33E/S37A mutants[1].
NRX-252262 induces mutant β-catenin degradation with an EC50 of 3.8 nM. At 35 μM, it effectively degrades S33E/S37A mutant β-catenin in cells. The compound's potent activity in promoting β-catenin degradation has been characterized in cellular assays. By directly strengthening the β-catenin–SCF^β-TrCP interface, NRX-252262 suppresses aberrant Wnt/β-catenin signaling. Its mechanism of action makes it a valuable tool for studying β-catenin turnover and degradation strategies. |
| ln Vivo |
In vivo activity data for NRX-252262 are not extensively reported. The compound is a valuable tool for studying β-catenin turnover, validating β-catenin degradation strategies, and exploring therapeutic concepts in Wnt-driven cancers and related pathologies. Further research is needed to evaluate its pharmacokinetic properties and efficacy in animal models. The compound's targeted mechanism of action suggests potential for in vivo studies in Wnt-driven cancers.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for NRX-252262 typically involves a protein-protein interaction assay to measure its ability to enhance the β-catenin–SCF^β-TrCP interaction. Recombinant β-catenin and SCF^β-TrCP components are incubated with varying concentrations of NRX-252262, and the enhancement of binding is measured using surface plasmon resonance (SPR), AlphaScreen, or ELISA-based methods. Ubiquitination assays using recombinant proteins can also be performed to measure the compound's ability to promote β-catenin ubiquitination.
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| Cell Assay |
The in vitro cellular assay for NRX-252262 typically uses cells expressing mutant β-catenin, such as S33E/S37A mutants. Cells are treated with varying concentrations of NRX-252262, and β-catenin protein levels are measured by Western blot to assess degradation. Ubiquitination of β-catenin can be assessed by immunoprecipitation followed by Western blot for ubiquitin. Wnt/β-catenin target gene expression is measured by qPCR or Western blot to confirm suppression of downstream signaling. Cell viability and proliferation are assessed using standard assays.
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| Animal Protocol |
In vivo animal studies for NRX-252262 are not extensively documented. For compounds targeting β-catenin degradation, typical in vivo models include xenograft tumor models in mice, particularly using cancer cell lines with mutant β-catenin. Mice bearing subcutaneous tumors would be treated with NRX-252262, and tumor growth inhibition, β-catenin protein levels, and Wnt target gene expression would be assessed. However, specific protocols for NRX-252262 have not been reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for NRX-252262 are not available in the public domain. The compound has a molecular weight of 545.36 and a formula of C23H17Cl2F3N2O4S. As a research tool, detailed ADME parameters including absorption, distribution, metabolism, and excretion have not been characterized. Researchers should perform their own pharmacokinetic studies if in vivo application is intended.
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| Toxicity/Toxicokinetics |
Toxicity data for NRX-252262 are not available in the public domain. As a research compound, comprehensive toxicological evaluations have not been performed. The compound is intended for laboratory research use only and should be handled with standard safety precautions. Appropriate personal protective equipment should be worn when handling this compound. Consult the Material Safety Data Sheet for specific safety and handling information.
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| References | |
| Additional Infomation |
NRX-252262 is a potent enhancer of β-catenin–SCF^β-TrCP interaction that promotes ubiquitination and proteasomal degradation of mutant β-catenin (EC50 = 3.8 nM). It directly strengthens the β-catenin–E3 ligase interface rather than inhibiting upstream regulators. The compound is a valuable tool for studying β-catenin turnover, validating degradation strategies, and exploring therapeutic concepts in Wnt-driven cancers. NRX-252262 is not in clinical trials and has not been approved for therapeutic use. It remains a research tool for studying β-catenin biology and Wnt signaling.
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| Molecular Formula |
C23N2O4F3SCL2H17
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|---|---|
| Molecular Weight |
545.36
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| Exact Mass |
544.023
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| CAS # |
2438637-61-5
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| PubChem CID |
138319682
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| Appearance |
White to off-white solid powder
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| Density |
1.57±0.1 g/cm3(Predicted)
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| Boiling Point |
628.7±55.0 °C(Predicted)
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
886
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2CN(CC2=C1)C(=O)C3=C(C=C(NC3=O)C(F)(F)F)SC4=C(C=CC=C4Cl)Cl)OC
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| InChi Key |
SPAYLOCXFWJEBL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H17Cl2F3N2O4S/c1-33-15-6-11-9-30(10-12(11)7-16(15)34-2)22(32)19-17(8-18(23(26,27)28)29-21(19)31)35-20-13(24)4-3-5-14(20)25/h3-8H,9-10H2,1-2H3,(H,29,31)
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| Chemical Name |
4-(2,6-dichlorophenyl)sulfanyl-3-(5,6-dimethoxy-1,3-dihydroisoindole-2-carbonyl)-6-(trifluoromethyl)-1H-pyridin-2-one
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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: 8.33 mg/mL (15.27 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8337 mL | 9.1683 mL | 18.3365 mL | |
| 5 mM | 0.3667 mL | 1.8337 mL | 3.6673 mL | |
| 10 mM | 0.1834 mL | 0.9168 mL | 1.8337 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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