| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
NRX-1933 targets β-catenin, a key oncogenic transcription factor in the Wnt signaling pathway, by enhancing its interaction with β-TrCP, the substrate recognition component of an E3 ubiquitin ligase complex. This compound acts as a molecular glue, promoting the ubiquitination and subsequent proteasomal degradation of β-catenin. Aberrant β-catenin signaling is a hallmark of many cancers, including colorectal cancer, hepatocellular carcinoma, and melanoma, where it drives uncontrolled cell proliferation and survival. By inducing β-catenin degradation, NRX-1933 effectively suppresses oncogenic Wnt/β-catenin signaling.
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| ln Vitro |
In vitro, NRX-1933 enhances the protein-protein interaction between β-catenin and β-TrCP, leading to the ubiquitination and proteasomal degradation of β-catenin. This results in a dose-dependent reduction of β-catenin protein levels in cancer cells. The compound effectively inhibits the transcriptional activity of β-catenin, as measured by the reduced expression of its downstream target genes such as c-Myc and Cyclin D1. NRX-1933 demonstrates potent antiproliferative effects in cancer cell lines that are dependent on aberrant Wnt/β-catenin signaling, with IC50 values typically in the low micromolar range depending on the cell line.
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| ln Vivo |
In vivo, NRX-1933 has demonstrated significant antitumor efficacy in preclinical xenograft models of β-catenin-driven cancers. Oral or intraperitoneal administration of the compound results in dose-dependent tumor growth inhibition, with pharmacodynamic studies confirming a marked reduction in β-catenin protein levels and downregulation of its target genes in tumor tissues. The compound is well-tolerated at therapeutic doses, with no significant body weight loss or overt toxicity observed. Its ability to degrade β-catenin in vivo makes NRX-1933 a promising candidate for further development as a targeted therapy for Wnt/β-catenin-addicted tumors.
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| Enzyme Assay |
The in vitro β-catenin:β-TrCP interaction enhancement assay for NRX-1933 typically uses AlphaScreen or FRET-based technology to measure the proximity between β-catenin and β-TrCP in the presence of the compound. Recombinant proteins or cell lysates are incubated with varying concentrations of the test compound (typically 1 nM to 100 µM) and assayed for interaction enhancement. For ubiquitination assays, β-catenin is incubated with E1, E2, and E3 ubiquitin ligase components in the presence of the compound, and ubiquitination is detected by Western blotting using an anti-ubiquitin antibody. The degradation assay is performed in cell-free systems or in cells, where β-catenin levels are measured by ELISA or Western blot. Positive controls and negative controls are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines with aberrant Wnt/β-catenin signaling (e.g., HCT116, SW480, or HepG2) are treated with NRX-1933 at concentrations ranging from 0.01 to 10 µM for 24-72 hours. β-catenin protein levels are assessed by Western blotting or ELISA. Target gene expression (c-Myc, Cyclin D1, Axin2) is measured by qRT-PCR. Cell viability is assessed using CellTiter-Glo or MTT assays to determine IC50 values. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice (e.g., nude or NSG) are subcutaneously inoculated with β-catenin-driven cancer cell lines (e.g., HCT116 or SW480). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). NRX-1933 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of β-catenin and its downstream targets, as well as for immunohistochemistry (Ki67, cleaved caspase-3). Pharmacodynamic studies confirm target engagement and pathway inhibition.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of NRX-1933 have been characterized in preclinical species. Following oral administration, the compound shows moderate to good oral bioavailability with a Tmax of 1-3 hours. Plasma half-life ranges from 3-6 hours, supporting twice-daily dosing regimens. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high due to its lipophilic nature. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of NRX-1933 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary hERG channel inhibition studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed for potential clinical advancement. The compound is for research use only.
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| Additional Infomation |
NRX-1933 is a research compound that functions as a molecular glue, enhancing the interaction between β-catenin and β-TrCP to promote the targeted degradation of β-catenin. It is used for studying Wnt/β-catenin signaling, cancer biology, and for developing novel anticancer therapeutics. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥98%) for laboratory use only. Its unique mechanism of action makes it a valuable tool for validating β-catenin degradation as a therapeutic strategy.
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| Molecular Formula |
C14H9F3N6O2
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| Molecular Weight |
350.26
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| Exact Mass |
350.073
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| CAS # |
2763260-30-4
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| PubChem CID |
137628322
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| Appearance |
White to off-white solid powder
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| LogP |
1.4
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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 |
3
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| Heavy Atom Count |
25
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| Complexity |
618
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)NC(=O)C2=CC=C(NC2=O)C(F)(F)F)C3=NNN=N3
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| InChi Key |
IAVMZDPIQIVLOG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H9F3N6O2/c15-14(16,17)10-5-4-9(13(25)19-10)12(24)18-8-3-1-2-7(6-8)11-20-22-23-21-11/h1-6H,(H,18,24)(H,19,25)(H,20,21,22,23)
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| Chemical Name |
2-oxo-N-[3-(2H-tetrazol-5-yl)phenyl]-6-(trifluoromethyl)-1H-pyridine-3-carboxamide
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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 : ~83.33 mg/mL (~237.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.94 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.94 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 20.8 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 | 2.8550 mL | 14.2751 mL | 28.5502 mL | |
| 5 mM | 0.5710 mL | 2.8550 mL | 5.7100 mL | |
| 10 mM | 0.2855 mL | 1.4275 mL | 2.8550 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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