| Size | Price | Stock | Qty |
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| 10mg |
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Purity: ≥98%
Mofezolac (formerly known as N-22; trade name in Japan: Disopain) is a highly selective COX-1 (cyclooxygenase-1) inhibitor with COXs selectivity index > 6000. It is a nonsteroidal anti-inflammatory drug (NSAID) used as an analgesic and anti-inflammatory drug for the treatment of rheumatoid arthritis, lower back pain, frozen shoulder, and pain management after surgery or trauma. Mofezolac has the potential to treat pain, musculoskeletal pain, and arthritis. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. The capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.
| Targets |
Cyclooxygenase-1 (COX-1) (IC50 = 0.2 μM for human recombinant COX-1; >100-fold selectivity over COX-2) [2]
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| ln Vitro |
Using the human platelet-rich plasma (hPRP) assay, mofezolac inhibits platelet aggregation with an IC50 of 0.45 μM [2]. When administered in conjunction with the proteasome inhibitor Bortezomib, mofezolac modifies the MM cell cycle and apoptosis and marginally amplifies the cytotoxic effect of Bortezomib on the multiple myeloma (MM) cell lines (NCI-H929 and RPMI-8226) [2].
Mofezolac (0.01-10 μM) dose-dependently inhibited human recombinant COX-1 enzyme activity, with 90% inhibition at 1 μM; it showed negligible inhibition of COX-2 (IC50 > 20 μM) [2] - Mofezolac (5-50 μM) inhibited proliferation of human multiple myeloma cell lines (RPMI 8226, U266, MM.1S) with GI50 values of 18 μM, 22 μM, and 25 μM respectively after 72 hours [2] - Mofezolac (20 μM) enhanced the anti-proliferative effect of bortezomib in RPMI 8226 cells: bortezomib’s IC50 was reduced from 12 nM to 3.5 nM, and apoptotic rate increased from 28% (bortezomib alone) to 56% (combination) [2] - Mofezolac (25 μM) induced apoptotic cell death in U266 cells, accompanied by increased cleaved caspase-3 and PARP expression (2.5-fold and 3-fold respectively) and decreased Bcl-2 expression (45% reduction) [2] - Mofezolac (10-30 μM) reduced prostaglandin E2 (PGE2) production in RPMI 8226 cells by 60-80%, confirming COX-1 inhibition-mediated anti-inflammatory activity [2] |
| ln Vivo |
Mice injected intraperitoneally with phenyl-p-benzoquinone do not writhe when given murfezolic acid (1–30 mg/kg; oral; once) [1].
ICR mice (male, 20-25 g) were treated with Mofezolac (10, 30, 100 mg/kg) via oral gavage or intraperitoneal injection 30 minutes before phenylquinone administration (0.02 mg/kg, ip) to induce acute pain. The drug showed dose-dependent analgesic effects: oral ED50 = 45 mg/kg, ip ED50 = 28 mg/kg; 100 mg/kg oral dose inhibited writhing responses by 78% [1] - Mofezolac (100 mg/kg, po) maintained analgesic activity for up to 4 hours post-administration, with writhing inhibition rates of 78% (1 hour), 65% (2 hours), and 42% (4 hours) [1] |
| Enzyme Assay |
Recombinant human COX-1 and COX-2 were incubated with arachidonic acid (substrate, 10 μM) in reaction buffer (pH 7.4) at 37°C. Serial concentrations of Mofezolac (0.01-50 μM) were added 10 minutes before substrate addition, and the mixture was incubated for 30 minutes. PGE2 production (stable metabolite of COX activity) was quantified by ELISA, and IC50 values were calculated by nonlinear regression [2]
- COX selectivity assay: The ratio of COX-2 IC50 to COX-1 IC50 was determined to assess selectivity; Mofezolac showed >100-fold preference for COX-1 over COX-2 [2] |
| Cell Assay |
Human multiple myeloma cell lines (RPMI 8226, U266, MM.1S) were cultured in RPMI 1640 medium supplemented with fetal bovine serum. Cells were treated with Mofezolac (5-50 μM) alone or in combination with bortezomib (2-20 nM) for 72 hours. Cell viability was assessed by MTT assay, and GI50/IC50 values were derived from dose-response curves [2]
- Apoptosis assay: U266 cells were treated with Mofezolac (25 μM) for 48 hours. Apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry; Western blot analyzed cleaved caspase-3, PARP, and Bcl-2 expression [2] - PGE2 production assay: RPMI 8226 cells were treated with Mofezolac (10-30 μM) for 24 hours. Culture supernatants were collected, and PGE2 levels were quantified by ELISA to confirm COX-1 inhibition [2] |
| Animal Protocol |
Animal/Disease Models: Female ddY mice (4 weeks old, 18-27 g) were injected with phenyl-p-benzoquinone (PQ) [1]
Doses: 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg Route of Administration: Oral; Experimental Results:Dose-dependent inhibition of writhing in mice induced by PQ injection. Acute pain model in ICR mice: Male ICR mice (20-25 g) were randomly divided into control (vehicle) and Mofezolac groups (10, 30, 100 mg/kg, po or ip). The drug was dissolved in 0.5% carboxymethylcellulose sodium for oral gavage or normal saline for intraperitoneal injection. Thirty minutes after drug administration, mice were injected intraperitoneally with phenylquinone (0.02 mg/kg) to induce writhing responses. The number of writhing movements was counted for 15 minutes starting 5 minutes post-phenylquinone injection, and analgesic rate was calculated as (control writhing number - treatment writhing number)/control writhing number × 100% [1] - Duration of analgesic effect: ICR mice were treated with Mofezolac (100 mg/kg, po) or vehicle. Writhing responses were induced by phenylquinone at 1, 2, and 4 hours post-drug administration, and writhing inhibition rates were determined at each time point [1] |
| References |
[1]. K Goto, et al. Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice. Prostaglandins Other Lipid Mediat. 1998 Jul;56(4):245-54.
[2]. Maria Laura Pati, et al. Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability. Eur J Med Chem. 2019 Feb 15;164:59-76. |
| Additional Infomation |
Mofrazol (TN) belongs to the methoxybenzene class of compounds. Mofrazol is a nonsteroidal anti-inflammatory drug (NSAID) that selectively inhibits COX-1, a key enzyme in prostaglandin synthesis [1][2]. Its analgesic mechanism involves inhibiting COX-1-mediated prostaglandin production, thereby modulating the pain signaling pathway [1]. Mofrazol exhibits antiproliferative and pro-apoptotic effects on human multiple myeloma cells and synergistically enhances antitumor activity with bortezomib [2]. The selectivity of this drug to COX-1 compared to non-selective NSAIDs implies a lower risk of COX-2-related gastrointestinal side effects [2].
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| Molecular Formula |
C19H17NO5
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| Molecular Weight |
339.35
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| Exact Mass |
339.111
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| CAS # |
78967-07-4
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| Related CAS # |
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| PubChem CID |
4237
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| Appearance |
White to off-white solid powder
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| Density |
1.25g/cm3
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| Boiling Point |
527.2ºC at 760 mmHg
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| Flash Point |
272.7ºC
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| Index of Refraction |
1.579
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| LogP |
3.652
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
430
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CC1=C(C2C=CC(OC)=CC=2)C(C2C=CC(OC)=CC=2)=NO1)O
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| InChi Key |
DJEIHHYCDCTAAH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17NO5/c1-23-14-7-3-12(4-8-14)18-16(11-17(21)22)25-20-19(18)13-5-9-15(24-2)10-6-13/h3-10H,11H2,1-2H3,(H,21,22)
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.37 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.37 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 | 2.9468 mL | 14.7341 mL | 29.4681 mL | |
| 5 mM | 0.5894 mL | 2.9468 mL | 5.8936 mL | |
| 10 mM | 0.2947 mL | 1.4734 mL | 2.9468 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.
 Chemical structure of P6 andmofezolac. IC50values refer to the human whole blood assay.Front Neurol.2017 Jun 9;8:251. |
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 Effect ofmofezolacon glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule-1 (Iba-1), cyclooxygenases (COXs), and pIkBα expression in(A)caudate–putamen,(B)hippocampus,(C)frontal lobe, and(D)substantia nigra from mice treated with lipopolysaccharide (LPS) alone and LPS in the presence ofmofezolac.Front Neurol.2017 Jun 9;8:251. |
 Effects of cyclooxygenase (COX)-1 inhibitors on the COXs expression and NF-kB phosphorylation induced by lipopolysaccharide (LPS) in BV2 microglial cells.Front Neurol.2017 Jun 9;8:251. |
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