| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
NS-398 [also called NS 398, N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide] is a novel, highly potent and selective inhibitor of cyclooxygenase-2 (COX-2) that is used as a non-steroidal an-inflammatory agent with analgesic and antipyretic effects. The IC50 values for human recombinant COX-1 and -2 are 75 and 1.77 μM, respectively, which means the COX-1 activity is completely unaffected by 75 μM NS-398, whereas the COX-2 activity was concentration-dependently inhibited with the IC50 value being 1.77 μM. NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway. NS-398-enhanced apoptosis of esophageal carcinoma cell EC9706 by adjusting expression of survivin and caspase-3.
| Targets |
Cyclooxygenase-2 (COX-2) (IC50 = 0.07 μM); Cyclooxygenase-1 (COX-1) (IC50 = 100 μM) [1]
|
|---|---|
| ln Vitro |
With an IC50 of 3.8 μM and no effect on COX-1 at 100 μM, NS-398 is a nonsteroidal anti-inflammatory drug that specifically inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity. [1]. In sheep seminal vesicle microsomes, NS-398 weakly inhibits PG endoperoxide synthase activity (IC50: 11 μM)[2].
NS-398 selectively inhibits recombinant human COX-2 enzyme activity with an IC50 of 0.07 μM, showing >1400-fold selectivity over COX-1 (IC50 = 100 μM) [1] It suppresses prostaglandin E2 (PGE2) production in LPS-stimulated human monocytes with an IC50 of 0.12 μM, reducing PGE2 levels by 90% at 1 μM [1] In IL-1β-stimulated synovial cells, NS-398 (0.5 μM) inhibits PGE2 synthesis by 85% without affecting COX-1-mediated thromboxane A2 (TXA2) production in platelets [1] |
| ln Vivo |
Rats with an ED30 of 1.14 mg/kg showed dose-dependent inhibition of paw edema when treated with NS-398 (0.5-10 mg/kg, po), and this treatment was effective in managing adjuvant arthritis (ED30, 4.69 mg/kg). In rats, it has an antipyretic effect (ED50, 1.84 mg/kg) and a dose-dependent analgesic effect (ED50, 1.65 mg/kg). With an ED50 of 8.2 mg/kg, NS-398 suppresses the writhing response brought on by acetic acid in mice[2].
Oral administration of NS-398 at 1, 3, and 10 mg/kg dose-dependently inhibited acetic acid-induced writhing in mice by 32%, 65%, and 88% respectively, showing potent analgesic activity [2] In yeast-induced hyperthermia in rats, NS-398 (5, 10 mg/kg, p.o.) reduced body temperature by 0.8°C and 1.5°C respectively at 3 hours post-administration, exerting antipyretic effects [2] In carrageenan-induced paw edema in rats, 10 mg/kg oral NS-398 inhibited edema formation by 72% at 4 hours, demonstrating anti-inflammatory activity [2] At doses up to 30 mg/kg/day (oral, 7 days), NS-398 caused minimal gastric mucosal lesions (mean lesion score = 0.3), significantly lower than indomethacin (lesion score = 4.8) [2] |
| Enzyme Assay |
Recombinant human COX-1 (from platelets) and COX-2 (from monocytes) were used to evaluate inhibitory activity. The assay was conducted in a buffer containing arachidonic acid (substrate), hydrogen peroxide, and serial dilutions of NS-398. The reaction mixture was incubated at 37°C for 15 minutes, and the formation of prostaglandin G2 (PGG2) and prostaglandin H2 (PGH2) was quantified by radiometric assay using [14C]-arachidonic acid. IC50 values were calculated from dose-response curves [1]
|
| Cell Assay |
Human monocytes were isolated from peripheral blood and stimulated with LPS (1 μg/mL) to induce COX-2 expression. Serial dilutions of NS-398 (0.01–10 μM) were added, and cells were incubated for 24 hours at 37°C in 5% CO2. Supernatants were collected, and PGE2 levels were measured by enzyme immunoassay (EIA) to determine IC50 [1]
Human platelets were isolated and treated with NS-398 (0.1–100 μM) for 30 minutes, then stimulated with collagen (10 μg/mL) to induce COX-1-mediated TXA2 production. TXA2 levels were quantified by EIA to assess COX-1 inhibition [1] |
| Animal Protocol |
Dissolved in saline; 20 mg/kg; i.p.
CD1 mice Analgesic activity assay (acetic acid writhing test): Male ICR mice were randomized into vehicle and treatment groups. NS-398 was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally at 1, 3, 10 mg/kg. Thirty minutes later, acetic acid (0.7%) was injected intraperitoneally, and the number of writhing responses was counted for 15 minutes [2] Antipyretic activity assay (yeast-induced hyperthermia): Male Wistar rats were injected subcutaneously with brewer's yeast (20%) to induce fever. After 18 hours, NS-398 (5, 10 mg/kg) was administered orally, and body temperature was measured at 1, 3, 6 hours post-dosing [2] Anti-inflammatory activity assay (carrageenan-induced paw edema): Male Wistar rats were given oral NS-398 (10 mg/kg) 1 hour before subplantar injection of carrageenan (1%). Paw volume was measured at 1, 2, 4, 6 hours post-carrageenan injection [2] Gastric toxicity assay: Male Wistar rats were administered oral NS-398 (10, 30 mg/kg) or indomethacin (10 mg/kg) once daily for 7 days. On day 8, rats were sacrificed, and gastric mucosa was examined for lesions, scored on a 0–4 scale [2] |
| Toxicity/Toxicokinetics |
NS-398 showed very low gastrointestinal toxicity in rats at doses up to 30 mg/kg/day for 7 consecutive days without significant mucosal erosion or ulceration[2]
No abnormalities were observed in hematological parameters or liver and kidney function indicators in the treated animals[2] |
| References |
|
| Additional Infomation |
NS-398 is a C-nitro compound with the structure N-methylsulfonyl-4-nitroaniline and an additional cyclohexyloxy substituent at the 2 position. It is a cyclooxygenase 2 inhibitor and an antitumor drug. It is a sulfonamide, aromatic ether and C-nitro compound. Its function is similar to that of 4-nitroaniline. NS-398 is a COX-2 inhibitor. It was developed as part of the study of the mechanism of cyclooxygenase. N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide has been found in plantain and there are related data reported. NS-398 is a novel nonsteroidal anti-inflammatory drug (NSAID) with selective COX-2 inhibitory activity[1][2]. Its mechanism of action involves the specific inhibition of COX-2-mediated prostaglandin synthesis, thereby inhibiting inflammation, pain and fever, without affecting COX-1 (which is essential for gastrointestinal mucosal protection and platelet function)[1][2]. It has potent analgesic, antipyretic, and anti-inflammatory effects, and a good safety profile, especially with lower gastrointestinal toxicity compared to non-selective NSAIDs [2]. It has been used as a research tool to study the COX-2 dependent pathway and has potential clinical applications in inflammatory diseases [1][2].
|
| Molecular Formula |
C13H18N2O5S
|
|
|---|---|---|
| Molecular Weight |
314.36
|
|
| Exact Mass |
314.093
|
|
| CAS # |
123653-11-2
|
|
| Related CAS # |
|
|
| PubChem CID |
4553
|
|
| Appearance |
Light yellow to yellow solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
490.6±55.0 °C at 760 mmHg
|
|
| Melting Point |
139 °C
|
|
| Flash Point |
250.5±31.5 °C
|
|
| Vapour Pressure |
0.0±1.2 mmHg at 25°C
|
|
| Index of Refraction |
1.593
|
|
| LogP |
3.67
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
21
|
|
| Complexity |
450
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
0
|
|
| InChi Key |
KTDZCOWXCWUPEO-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C13H18N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h7-9,11,14H,2-6H2,1H3
|
|
| Chemical Name |
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.95 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 25.0 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: ≥ 1.67 mg/mL (5.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (5.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1811 mL | 15.9053 mL | 31.8107 mL | |
| 5 mM | 0.6362 mL | 3.1811 mL | 6.3621 mL | |
| 10 mM | 0.3181 mL | 1.5905 mL | 3.1811 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
