Cimicoxib  (Synonyms: UR-8880)

Cimicoxib (UR-8880) is an orally active, blood-brain barrier-permeable COX-2 inhibitor that also exerts targeted inhibition on CYP2D15. It has an IC₅₀ of 66 nM against hCOX-2, an IC₅₀ of 1.6 μM against canine CYP2D15, and an IC₅₀ of 0.056 μM against feline CYP2D15. By inhibiting the COX-2 pathway to reduce the production of thromboxane B2 and prostaglandin E2, Cimicoxib exerts antipyretic, anti-inflammatory and analgesic effects. Cimicoxib is metabolized by CYP2D15 to form demethyl-cimicoxib, undergoes glucuronidation via UDP-glucuronosyltransferases, and exhibits biphasic elimination kinetics in beagle dogs. Cimicoxib is widely used in studies of inflammatory diseases, osteoarthritis, and perioperative pain associated with orthopedic or soft tissue surgeries^[1][2][3][4].

Cimicoxib (15 μM; 30 min) undergoes phase 1 metabolism to form demethyl-cimicoxib in feline hepatic microsomes, with CYP2D15 as the primary metabolizing enzyme and CYP3A12 contributing to a lesser extent, and has lower affinity for feline CYP2D15 orthologs than for canine CYP2D15^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cimicoxib (2 mg/kg; i.v.; single slow bolus injection) administered as a single 2 mg/kg i.v. bolus in healthy Beagle dogs has a total body clearance of 0.49 L/h kg, a terminal half-life of 1.90 h, and 12.17% of the dose is eliminated in urine primarily as conjugated demethyl-cimicoxib^[2].
Cimicoxib (1 mg/kg; i.v.; single slow bolus injection) administered as a single 1 mg/kg i.v. bolus in healthy European crossbreed cats has a total body clearance of 0.13 L/h kg, a terminal half-life of 5.16 h, and 3.32% of the dose is eliminated in urine with conjugated demethyl-cimicoxib representing the majority of urinary metabolites^[2].
Cimicoxib (2 mg/kg; p.o., i.v.; single dose) exhibits significant antipyretic, anti-inflammatory, and analgesic efficacy in beagle dogs with kaolin-induced paw inflammation, with EM dogs requiring lower plasma concentrations for half-maximal effects and PM dogs demonstrating longer effect durations^[3].
Cimicoxib (2-5 mg/kg; p.o. via nasogastric tube; single dose) produces mean maximal COX-1 inhibition of 62.4% (fasted) and 54.6% (fed), and mean maximal COX-2 inhibition of 72.1% (fasted) and 68.5% (fed) in healthy mares at the 5 mg/kg dose, while the 2 mg/kg dose yields detectable plasma concentrations but no reported specific inhibition values^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

381.81

C₁₆H₁₃ClFN₃O₃S

265114-23-6

Solid

White to off-white

O=S(C1=CC=C(N2C(C3=CC=C(OC)C(F)=C3)=C(Cl)N=C2)C=C1)(N)=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Pawar V G, et al. Synthesis of 1, 5-disubstituted 4-haloimidazoles from α-aminonitriles[J]. Tetrahedron letters, 2006, 47(31): 5451-5453.

  [2]. Schneider M, et al. Comparative pharmacokinetic profile of cimicoxib in dogs and cats after IV administration. Vet J. 2021;270:105625.

  [3]. Jeunesse EC, et al. Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog. BMC Vet Res. 2013;9:250. Published 2013 Dec 11.  [Content Brief]

  [4]. Kim TW, et al. Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in fasted and fed horses. N Z Vet J. 2015;63(2):92-97.  [Content Brief]