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.

Physicochemical Properties

Molecular Formula	C19H17NO5
Molecular Weight	339.35
Exact Mass	339.111
CAS #	78967-07-4
Related CAS #	78967-07-4
PubChem CID	4237
Appearance	White to off-white solid powder
Density	1.25g/cm3
Boiling Point	527.2ºC at 760 mmHg
Flash Point	272.7ºC
Index of Refraction	1.579
LogP	3.652
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	430
Defined Atom Stereocenter Count	0
SMILES	O=C(CC1=C(C2C=CC(OC)=CC=2)C(C2C=CC(OC)=CC=2)=NO1)O
InChi Key	DJEIHHYCDCTAAH-UHFFFAOYSA-N
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)
Chemical Name	2-(3,4-bis(4-methoxyphenyl)isoxazol-5-yl)acetic acid
Synonyms	N-22; N 22; N22; Mofezolac; Disopain
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)

Biological Activity

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].
ln Vivo	Mice injected intraperitoneally with phenyl-p-benzoquinone do not writhe when given murfezolic acid (1–30 mg/kg; oral; once) [1].
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.
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	Mofezolac (TN) is a member of methoxybenzenes.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mM Water:< 1 mg/mL Ethanol:< 1 mg/mL

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. 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. 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	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.