| 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: 62 nM (β-catenin:β-TrCP Interaction)[1] Kd: 0.6 nM (β-catenin:β-TrCP Interaction)[1]
NRX-103094 targets the protein-protein interaction between β-catenin and the E3 ubiquitin ligase SCFβ-TrCP, specifically binding at the interface to enhance the recognition of phosphorylated β-catenin by β-TrCP. |
|---|---|
| ln Vitro |
With an EC50 of 457 nM, NRX-103094 demonstrates excellent efficacy with pSer33/Ser37 β-catenin peptide. At 250 nM, NRX-103094 increases the ubiquitylation of the β-catenin peptide of pSer33/S37A to a level higher than that of wild-type pSer33/pSer37. When 40 μM of the compound is present, NRX-103094 increases the S33E/S37A phosphomimetic peptide binding affinity for β-TrCP from >5 μM in the absence of the molecule to 22 nM. Robust time-dependent ubiquitylation of the S33E/S37A β-catenin peptide is detected in the presence of 20 μM NRX-103094. Similarly, in the presence of 20 μM NRX-103094, the full-length S33E/S37A β-catenin protein exhibits substantial ubiquitylation, with ubiquitylation levels that are similar to those of the WT full-length β-catenin protein[1].
NRX-103094 enhances the binding of pSer33/Ser37 β-catenin peptide to β-TrCP with an EC₅₀ of 62 nM and a Kd of 0.6 nM. It demonstrates excellent efficacy in promoting the interaction between β-catenin and its cognate E3 ligase. At 250 nM, NRX-103094 increases the ubiquitylation of the β-catenin peptide of pSer33/S37A to a level higher than that of wild-type pSer33/pSer37. |
| ln Vivo |
In vivo activity data for NRX-103094 has not been extensively reported. As a molecular glue that enhances β-catenin ubiquitination, it has the potential to promote the degradation of β-catenin in cellular and potentially in vivo settings.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for NRX-103094 typically involve cell-free systems using purified β-TrCP protein and phosphorylated β-catenin peptide. The compound is incubated with the protein-peptide complex, and binding affinity is measured using techniques such as surface plasmon resonance or fluorescence polarization. EC₅₀ and Kd values are determined from dose-response binding curves.
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| Cell Assay |
For in vitro cellular experiments, NRX-103094 is dissolved in DMSO and diluted in cell culture medium. Cells are treated with the compound at varying concentrations, and the interaction between β-catenin and β-TrCP is assessed by co-immunoprecipitation or proximity ligation assays. Ubiquitination and degradation of β-catenin can be monitored by Western blot analysis. The compound's molecular glue activity can be evaluated by measuring the enhancement of β-catenin ubiquitination and subsequent proteasomal degradation.
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| Animal Protocol |
In vivo animal experiments with NRX-103094 would typically involve formulation in suitable vehicles for administration to mouse models. Dosing routes may include oral gavage, intraperitoneal injection, or intravenous administration. Pharmacodynamic endpoints would include measurement of β-catenin protein levels in target tissues, assessment of Wnt signaling activity, and evaluation of tumor growth inhibition in cancer xenograft models.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NRX-103094 have not been extensively characterized in public literature. The compound has a molecular formula of C₂₀H₁₁Cl₂F₃N₂O₄S and a molecular weight of 503.28. Standard PK studies would assess parameters such as half-life, oral bioavailability, and tissue distribution.
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| Toxicity/Toxicokinetics |
Toxicological data for NRX-103094 is limited to research applications. The compound is intended for laboratory use only and has not been evaluated for human therapeutic safety. Standard chemical handling precautions should be followed.
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| References | |
| Additional Infomation |
NRX-103094 is a potent enhancer of the interaction between β-catenin and SCFβ-TrCP. It belongs to the class of molecular glues that promote protein-protein interactions. The compound is used as a research tool to study β-catenin regulation and Wnt signaling pathways. No clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C20H11CL2F3N2O4S
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|---|---|
| Molecular Weight |
503.278552293777
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| Exact Mass |
501.976
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| CAS # |
2763260-36-0
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| PubChem CID |
137628320
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
839
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(O)(=O)C1=CC=CC(NC(C2=C(SC3=C(Cl)C=CC=C3Cl)C=C(C(F)(F)F)NC2=O)=O)=C1
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| InChi Key |
HFBGFWJURBVNFD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H11Cl2F3N2O4S/c21-11-5-2-6-12(22)16(11)32-13-8-14(20(23,24)25)27-18(29)15(13)17(28)26-10-4-1-3-9(7-10)19(30)31/h1-8H,(H,26,28)(H,27,29)(H,30,31)
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| Chemical Name |
3-[[4-(2,6-dichlorophenyl)sulfanyl-2-oxo-6-(trifluoromethyl)-1H-pyridine-3-carbonyl]amino]benzoic acid
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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 (99.35 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 | 1.9870 mL | 9.9348 mL | 19.8697 mL | |
| 5 mM | 0.3974 mL | 1.9870 mL | 3.9739 mL | |
| 10 mM | 0.1987 mL | 0.9935 mL | 1.9870 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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