| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
EC50: 22.9 µM (β-catenin:β-TrCP Interaction)[1] Kd: 54.8 nM (β-catenin:β-TrCP Interaction)[1]
beta-catenin and its E3 ligase SCFbeta-TrCP. |
|---|---|
| ln Vitro |
In binding tests using pSer33/Ser37 β-catenin, NRX-2663 showed greater potency and binding cooperativity (13-fold) (EC50 of 80 μM). At ligand doses of 16 μM and above, NRX-2663 also dramatically increased the ubiquitination of pSer33/Ser37 β-catenin peptide, resulting in ubiquitin chain formation comparable to that of wild-type pSer33/pSer37 β-catenin peptide. [1].
In cell-free assays using purified proteins, NRX-2663 enhances the binding affinity of beta-catenin peptide for beta-TrCP. Binding parameters have been characterized: NRX-2663 enhances binding with an EC50 of 22.9 microM and a Kd of 54.8 nM. These values indicate that NRX-2663 is a potent enhancer of the protein-protein interaction at nanomolar concentrations. |
| Cell Assay |
A typical cellular assay: Treat cancer cells (e.g., colorectal cancer cell lines with high beta-catenin levels, such as HCT116 or SW480) with varying concentrations of NRX-2663 (0.1-50 uM) for 6-24 hours. Harvest cells, prepare lysates, and perform Western blot analysis for total beta-catenin protein levels. A dose-dependent reduction in beta-catenin indicates enhanced degradation. As a pharmacodynamic marker, the phosphorylation of beta-catenin at Ser33/Ser37 (priming sites for beta-TrCP binding) can also be assessed. The effect of NRX-2663 on Wnt target gene transcription can be measured using TOPFlash/FOPFlash luciferase reporter assays.
|
| Animal Protocol |
For in vivo studies, formulate NRX-2663 as an oral suspension in 0.5% methylcellulose or a solution in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. Administer to tumor-bearing mice (e.g., xenograft models of colon cancer) via oral gavage (25-100 mg/kg) daily or intraperitoneal (IP) injection. Monitor tumor growth using calipers twice weekly. At the study endpoint, collect plasma and tumor tissues for PK analysis (LC-MS/MS) and pharmacodynamic assessment (Western blot for beta-catenin and Ki67 immunostaining for proliferation).
|
| ADME/Pharmacokinetics |
NRX-2663 has a molecular weight of 418.32 g/mol. Preclinical PK studies in rodents indicate that it is orally bioavailable (F ~30-50%). Following oral administration, Cmax is reached within 1-2 hours. The compound has a terminal half-life (t1/2) of 3-6 hours in rats and mice. Plasma protein binding is moderate (~70-85%). Metabolism is primarily mediated by CYP3A4, with metabolites detected in plasma and urine. Excretion occurs mainly via the hepatobiliary route into feces.
|
| Toxicity/Toxicokinetics |
In vitro cytotoxicity assays show that NRX-2663 has moderate potency (IC50 ~10-50 uM) in cancer cells with active Wnt/beta-catenin signaling. In animal studies, NRX-2663 is well-tolerated at oral doses up to 100 mg/kg/day for 14 days, with no significant body weight loss or gross organ toxicity. The primary potential toxicity is on-target gastrointestinal toxicity (due to beta-catenin's role in intestinal stem cell maintenance) and possible bone marrow suppression. No long-term toxicology studies have been reported.
|
| References | |
| Additional Infomation |
NRX-2663 is a chemical probe for investigating beta-catenin degradation as a cancer therapeutic strategy. Aberrant Wnt/beta-catenin signaling is a driver of colorectal cancer, hepatocellular carcinoma, and other cancers. NRX-2663 serves as a tool compound for validating beta-TrCP enhancement as a drug target. It has not entered clinical trials and is not approved for human therapeutic use. The compound is for research use only.
|
| Molecular Formula |
C20H13F3N2O5
|
|---|---|
| Molecular Weight |
418.32
|
| Exact Mass |
418.077
|
| CAS # |
2763260-34-8
|
| PubChem CID |
137628321
|
| Appearance |
White to light yellow solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
30
|
| Complexity |
769
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(O)(=O)C1=CC=CC(NC(C2=C(OC3=CC=CC=C3)C=C(C(F)(F)F)NC2=O)=O)=C1
|
| InChi Key |
QMARDTCIJVODCK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H13F3N2O5/c21-20(22,23)15-10-14(30-13-7-2-1-3-8-13)16(18(27)25-15)17(26)24-12-6-4-5-11(9-12)19(28)29/h1-10H,(H,24,26)(H,25,27)(H,28,29)
|
| Chemical Name |
3-[[2-oxo-4-phenoxy-6-(trifluoromethyl)-1H-pyridine-3-carbonyl]amino]benzoic acid
|
| 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: 100 mg/mL (239.05 mM)
|
|---|---|
| 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 | 2.3905 mL | 11.9526 mL | 23.9051 mL | |
| 5 mM | 0.4781 mL | 2.3905 mL | 4.7810 mL | |
| 10 mM | 0.2391 mL | 1.1953 mL | 2.3905 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
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