Parecoxib (SC69124A; Dynastat) is a selective cyclooxygenase-2 (COX-2) inhibitor with the potential for treating postoperative pain in adults. It is a water-soluble and injectable prodrug of valdecoxib.

Physicochemical Properties

Molecular Formula	C19H18N2O4S
Molecular Weight	370.42222
Exact Mass	370.098
CAS #	198470-84-7
Related CAS #	Parecoxib Sodium;198470-85-8;Parecoxib-d3
PubChem CID	119828
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Melting Point	148.9-151°
Index of Refraction	1.580
LogP	1.72
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	575
Defined Atom Stereocenter Count	0
InChi Key	TZRHLKRLEZJVIJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H18N2O4S/c1-3-17(22)21-26(23,24)16-11-9-14(10-12-16)18-13(2)25-20-19(18)15-7-5-4-6-8-15/h4-12H,3H2,1-2H3,(H,21,22)
Chemical Name	N-[4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)phenyl]sulfonylpropanamide
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	Parecoxib (0-200 μM; 24-48 hours) reduces the growth of GBM cells in a dose-dependent manner [4]. Parecoxib (200 μM; 24-48 hours) caused the migratory ability of U343 cells to be reduced compared with the PBS-treated group [4].
ln Vivo	In the elevated plus maze test, parecoxib (ip; 2.5, 5.0, or 10 mg/kg; once daily; 21 days) had no effect on locomotor activity; however, the percentage of time spent with arms outstretched was higher for parecoxib at doses of 5 and 10 mg/kg[3].
Cell Assay	Cell Viability Assay [4] Cell Types: GBM Cells: U251 and U343 Cell Tested Concentrations: 0 μM, 20 μM, 50 μM, 100 μM and 200 μM Incubation Duration: 24-48 hrs (hours) Experimental Results: Result in slower BrdU incorporation into GBM Cells include U251 and U343 cells.
Animal Protocol	Animal/Disease Models: Adult male ICR mouse, 15 weeks old, weighing 25-35 grams [3] Doses: 2.5, 5.0 or 10 mg/kg Route of Administration: intraperitoneal (ip) injection; 2.5, 5.0 or 10 mg/kg; one time/day; 21-day Experimental Results: Anxiolytic-like effects in the elevated plus maze test
ADME/Pharmacokinetics	Metabolism / Metabolites Hepatic. Metabolized primarily via CYP3A4 and 2C9 to valdecoxib and propionic acid. Biological Half-Life 22 minutes (parecoxib); 8 hours (valdecoxib)
Toxicity/Toxicokinetics	Protein Binding 98%
References	[1]. Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology. [2]. [Selective inhibitors of cyclooxygenase-2 (COX-2), celecoxib and parecoxib: a systematic review]. Drugs Today (Barc). 2010 Feb;46 Suppl A:1-25. [3]. Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice. BMC Anesthesiol. 2017 Nov 13;17(1):152. [4]. Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by upregulating miRNA-29c. Biol Open. 2017 Mar 15;6(3):311-316.
Additional Infomation	Parecoxib is an N-acylsulfonamide resulting from the formal condensation of valdecoxib with propionic acid. It is a prodrug for valdecoxib. It has a role as a cyclooxygenase 2 inhibitor, a non-narcotic analgesic, a non-steroidal anti-inflammatory drug and a prodrug. It is a member of isoxazoles and a N-sulfonylcarboxamide. It is functionally related to a valdecoxib. Parecoxib is a water-soluble and injectable prodrug of valdecoxib. It is marketed as Dynastat in the European Union. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib (Celebrex) and rofecoxib (Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac (Toradol) is used in the United States. A letter of non-approval for parecoxib was issued by the FDA in 2005. Parecoxib is an amide prodrug of the cyclooxygenase II (COX-2) selective, non-steroidal anti-inflammatory drug (NSAID) valdecoxib, with anti-inflammatory, analgesic, and antipyretic activities. Upon administration, parecoxib is hydrolyzed by hepatic carboxyesterases to its active form, valdecoxib. Valdecoxib selectively binds to and inhibits COX-2. This prevents the conversion of arachidonic acid into prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and, therefore, does not interfere with blood coagulation. Drug Indication Used for short term perioperative pain control. For the short-term treatment of postoperative pain in adults. , For the short-term treatment of postoperative pain. The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of theindividual patient's overall risks (see sections 4. 3, 4. 4). For the short-term treatment of postoperative pain.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~134.98 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 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 (6.75 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	2.6996 mL	13.4982 mL	26.9964 mL
	5 mM	0.5399 mL	2.6996 mL	5.3993 mL
	10 mM	0.2700 mL	1.3498 mL	2.6996 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.