Suprofen (R25061; TN762; R-25061; TN-762; Suprofen; Suprofenum; Profenal), a nonsteroid anti-inflammatory drug (NSAID), is a potent and nonselective dual inhibitor of COX-1/COX-2 enzymes with potential anti-inflammatory and antipyretic activity. It has been approved for use as a non-steroidal anti-inflammatory analgesic and antipyretic.

Physicochemical Properties

Molecular Formula	C14H12O3S
Molecular Weight	260.31
Exact Mass	260.05
CAS #	40828-46-4
Related CAS #	40828-46-4
PubChem CID	5359
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	442.6±30.0 °C at 760 mmHg
Melting Point	278ºC
Flash Point	221.5±24.6 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.613
LogP	2.42
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	18
Complexity	321
Defined Atom Stereocenter Count	0
InChi Key	MDKGKXOCJGEUJW-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H12O3S/c1-9(14(16)17)10-4-6-11(7-5-10)13(15)12-3-2-8-18-12/h2-9H,1H3,(H,16,17)
Chemical Name	2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid
Synonyms	R-25061;TN-762; R25061;TN 762; R 25061;TN762;Suprofen; Suprofenum; Profenal
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

Targets	Cyclooxygenase-1 (COX-1) [] [1][2] - Cyclooxygenase-2 (COX-2) [] [1][2]
ln Vitro	The NSAID Suprofen (TN-762) is used. Suprofen (TN-762) is an antipyretic and anti-inflammatory analgesic that works similarly to ibuprofen. It has been suggested that it possesses anti-arthritic properties and inhibits prostaglandin synthesis. 200 mg of prostanoids is preferred, saving 6-keto PGF1a[1].
ln Vivo	Suprofen combined with PGF2 alpha blocks induction of uterine contractions, suggesting the possibility that Suprofen also antagonizes PGF2 alpha receptor binding. Suprofen are effective at preventing BAB disruption after paracentesis in dogs, indicating their potential usefulness for treatment of prostaglandin-mediated ocular disease. Suprofen (3.7 mg/kg, i.v.) induces a marked decrease in the firing evoked in arthritic rats by ankle mobilization. In women with primary dysmenorrhea, oral administration of Suprofen (TN-762) (400 mg three times daily during menstruation) differentially suppressed menstrual fluid prostaglandins. It inhibited prostaglandin F2α (PGF2α) by 68%, prostaglandin E2 (PGE2) by 72%, 6-keto-prostaglandin F1α (6-keto-PGF1α) by 55%, and thromboxane B2 (TXB2) by 42% compared to baseline levels [2] - The suppression of prostaglandins was associated with a significant reduction in dysmenorrheal pain intensity, with 75% of patients reporting moderate to marked pain relief [2]
Animal Protocol	3.7 mg/kg, i.v. Rats Long-term safety study in rats: Male and female rats were randomly divided into control and Suprofen treatment groups (10, 30, 100 mg/kg/day). The drug was administered orally once daily for 6 months. Animals were monitored for general health status, body weight changes, food and water consumption. At the end of the study, blood samples were collected for hematological and biochemical analyses, and major organs (liver, kidney, stomach, intestines) were dissected for histopathological examination [1] - Long-term safety study in dogs: Beagle dogs were treated with Suprofen at oral doses of 5, 15, 45 mg/kg/day once daily for 6 months. Similar monitoring parameters as in rats were used, including clinical observations, body weight, hematology, serum biochemistry, and histopathological evaluation of organs [1]
ADME/Pharmacokinetics	Metabolism / Metabolites Primarily hepatic (mainly via cytochrome P450 isozyme 2C9). Suprofen has known human metabolites that include Thiophene-4,5-epoxide, (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[2-[4-(thiophene-2-carbonyl)phenyl]propanoyloxy]oxane-2-carboxylic acid, and Suprofen -sulfoxide.
Toxicity/Toxicokinetics	Protein Binding 20% In long-term animal studies (6 months), Suprofen at doses up to 100 mg/kg/day in rats and 45 mg/kg/day in dogs did not cause significant changes in body weight, hematological indices (red blood cells, white blood cells, platelets), or serum biochemical parameters (ALT, AST, creatinine, urea nitrogen) [1] - Mild gastrointestinal irritation (gastric mucosal hyperemia) was observed in rats at the highest dose (100 mg/kg/day) and dogs at 45 mg/kg/day, but no ulceration or severe lesions were found [1] - In human clinical use for primary dysmenorrhea, Suprofen showed mild and transient side effects, mainly gastrointestinal discomfort (nausea, abdominal cramps, diarrhea)[2]
References	[1]. Suprofen. An overview of long-term safety. Pharmacology, 1983. 27 Suppl 1: p. 87-94. [2]. Dawood, M.Y. and F.S. Khan-Dawood, Differential suppression of menstrual fluid prostaglandin F2a, prostaglandin E2, 6-keto prostaglandin F1a and thromboxane B2 by suprofen in women with primary dysmenorrhea. Prostaglandins Other Lipid Mediat, 2007. 83(1-2): p. 146-53.
Additional Infomation	Suprofen is an aromatic ketone that is thiophene substituted at C-2 by a 4-(1-carboxyethyl)benzoyl group. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, an antirheumatic drug, a peripheral nervous system drug and a drug allergen. It is a member of thiophenes, a monocarboxylic acid and an aromatic ketone. An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. It is no longer approved for use in the United States. An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. Drug Indication Used as eye drops to inhibit the miosis (pupil constriction) that may occur during ocular surgery. Mechanism of Action Suprofen binds to the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. The overall result is a reduction in pain and inflammation in the eyes and the prevention of pupil constriction during surgery. Normally trauma to the anterior segment of the eye (especially the iris) increases endogenous prostaglandin synthesis which leads to constriction of the iris sphincter. Pharmacodynamics Suprofen is a non-steroidal anti-inflammatory analgesic and antipyretic. Ophthalmic anti-inflammatory medicines are used in the eye to lessen problems that can occur during or after some kinds of eye surgery. Sometimes, the pupil of the eye gets smaller during an operation (pupil constriction), making it more difficult for the surgeon to reach some areas of the eye. Suprofen is used to help prevent this. Suprofen (TN-762) is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties, primarily indicated for the treatment of primary dysmenorrhea [1][2] - Its mechanism of action involves inhibiting cyclooxygenase enzymes (COX-1 and COX-2), thereby reducing the biosynthesis of prostaglandins that mediate pain and inflammation [1][2] - Long-term administration (up to 6 months) in animals showed good tolerability, with no cumulative toxicity or organ damage at therapeutic doses [1] - The drug exhibits differential suppression of various prostaglandins in menstrual fluid, with greater inhibition of PGE2 and PGF2α compared to 6-keto-PGF1α and TXB2 [2]

Solubility Data

Solubility (In Vitro)

DMSO:52 mg/mL (199.8 mM) Water:<1 mg/mL Ethanol:52 mg/mL (199.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.60 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 (9.60 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 (9.60 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	3.8416 mL	19.2079 mL	38.4157 mL
	5 mM	0.7683 mL	3.8416 mL	7.6831 mL
	10 mM	0.3842 mL	1.9208 mL	3.8416 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.