| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
It targets cyclooxygenase (COX) enzymes, inhibiting their activity and releasing NO. The released NO can down-regulate COX-2 expression. Additionally, it disrupts the proteasome-mediated degradation of I kappa B-alpha (IkappaB-alpha), thereby inhibiting NF-kappaB activation and subsequent inflammatory cytokine production.
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| ln Vitro |
In PC3 cells, NCX4040 dramatically increases the production of hydrogen peroxide, which causes oxidative stress and mitochondrial depolarization. These events result in lipid peroxidation, cell cycle arrest, inhibition of colony expansion, and induction of apoptosis [1]. NCX4040 (10-50 μM) depolymerizes F-actin and induces anoikis, which impairs PC3 cells' ability to migrate [1]. In PC3 cells, NCX4040 suppresses the expression of cyclin D1. Important anti-apoptotic markers, including survivin, X-linked inhibitor of apoptosis (XIAP), inhibitor of apoptosis protein 1 (cIAP1), and Cellular-Myc (c-Myc), were significantly downregulated, according to Western blot analysis[1]. Phosphohistone H2AX (pH2AX), cleaved caspase 3, and cleaved poly[ADP-ribose] polymerase 1 (PARP1) are all upregulated in cells treated with NCX4040- [1].
In isolated human monocytes, it blocks inflammatory mediator production with IC50 values of 0.07 microM (IL-1beta), 0.13 microM (PGE2), 0.15 microM (IL-10), and 0.18 microM (TNF-alpha). It decreases COX-2 expression (IC50 = 0.13 microM). It has antiproliferative effects in HCT116 colon cancer cells and induces apoptosis in PC3 metastatic prostate cancer cells. |
| ln Vivo |
NCX-4040 sensitizes drug-resistant human ovarian tumor cells to cisplatin. It has shown in vivo efficacy in reducing tumor size in xenograft models. It also has the ability to reverse drug-resistance in both ABCB1- and ABCG2-expressing multidrug-resistant human cancer cells.
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| Enzyme Assay |
For cell-free receptor binding studies, the proteasome is isolated via centrifugation, and the inhibition of IkappaB-alpha degradation is monitored. For COX inhibition, the enzyme is incubated with arachidonic acid and varying concentrations of NCX-4040 (0.01-10 microM) in Tris-HCl buffer. The reaction is stopped and PGE2 levels are quantified via ELISA to determine IC50 values.
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| Cell Assay |
For in vitro cell-based assays, PC3 prostate cancer cells or HCT116 colon cancer cells are seeded in 96-well plates and treated with increasing concentrations of NCX-4040 (0.1-100 uM) for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is confirmed via Annexin V-FITC/PI staining followed by flow cytometry. Cytokine levels (TNF-alpha, IL-1beta) in culture supernatants are measured by ELISA.
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| Animal Protocol |
For in vivo animal experiments, NCX-4040 is typically dissolved in DMSO and diluted in saline or other vehicle. For xenograft studies, immunocompromised mice bearing human tumor xenografts are treated intraperitoneally (IP) or intravenously (IV) with NCX-4040 (e.g., 25-50 mg/kg) daily for 14 days. Tumor volumes are measured biweekly. Blood is collected to assess NO levels and cytokine profiles.
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| ADME/Pharmacokinetics |
NCX-4040 (MW: 331.28) is soluble in DMSO (e.g., 15 mg/mL). It is stable for up to 3 years as a powder at -20degC and for 6 months in solution at -80degC. As an aspirin derivative, it is absorbed and metabolized to release NO and salicylic acid. Pharmacokinetic properties are typical of aspirin derivatives but NO release adds complexity.
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| Toxicity/Toxicokinetics |
NCX-4040 has shown favorable safety in preclinical models, but specific toxicological data beyond standard classification is limited. According to safety data, it is classified as Dangerous with hazard classifications including Aquatic Acute 1, Eye Dam. 1, and Skin Sens. 1.
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| References |
[1]. Somaiah Chinnapaka, et al. Nitro aspirin (NCX4040) induces apoptosis in PC3 metastatic prostate cancer cells via hydrogen peroxide (H 2 O 2)-mediated oxidative stress. Free Radic Biol Med. 2019 Nov 1;143:494-509.
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| Additional Infomation |
NCX-4040 was developed as a novel NSAID with reduced gastrointestinal toxicity due to NO donation. It is still in the preclinical research stage, not an approved drug. It is a valuable tool for studying the interplay between COX-2 and NO pathways in inflammation and cancer. It is for research use only.
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| Molecular Formula |
C16H13NO7
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|---|---|
| Molecular Weight |
331.27700
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| Exact Mass |
331.069
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| CAS # |
287118-97-2
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| PubChem CID |
9818919
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| Appearance |
White to off-white solid powder
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| LogP |
3.062
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
24
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)OC1=CC=CC=C1C(=O)OC2=CC=C(C=C2)CO[N+](=O)[O-]
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| InChi Key |
CTHNKWFUDCMLIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13NO7/c1-11(18)23-15-5-3-2-4-14(15)16(19)24-13-8-6-12(7-9-13)10-22-17(20)21/h2-9H,10H2,1H3
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| Chemical Name |
[4-(nitrooxymethyl)phenyl] 2-acetyloxybenzoate
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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 : ~100 mg/mL (~301.86 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.55 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 25.0 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 | 3.0186 mL | 15.0930 mL | 30.1859 mL | |
| 5 mM | 0.6037 mL | 3.0186 mL | 6.0372 mL | |
| 10 mM | 0.3019 mL | 1.5093 mL | 3.0186 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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