Background
Valdecoxib is a potent and selective inhibitor of cyclooxygenase-2 (COX-2) with IC50 value of 5nM [1].
Valdecoxib is developed for the management of pain and inflammation. Valdecoxib and its intravenous prodrug parecoxib exert significant opioid-sparing effects after dental, gynecologic, orthopedic and other noncardiac surgical procedures. In the cellular assay, valdecoxib shows inhibitory activity on human recombinant COX-2 with IC50 value of 5nM. It shows no significant effect on COX-1 with IC50 value of 140μM. In the ex vivo assay using human whole blood, valdecoxib prevents PGE2 production with IC50 value of 0.89μM. Moreover, oral administration of valdecoxib exerts chronic anti-inflammatory activity with ED50 value of 0.032 mg/kg/day in the rat adjuvant arthritis model. In addition, valdecoxib is reported to have cardiovascular risk adverse effect in patients undergoing CABG [1, 2].
参考文献:
[1] Talley J J, Brown D L, Carter J S, et al. 4-[5-Methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. Journal of medicinal chemistry, 2000, 43(5): 775-777.
[2] Nussmeier N A, Whelton A A, Brown M T, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. New England Journal of Medicine, 2005, 352(11): 1081-1091.
Protocol
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In vitro experiment [1]:
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Samples
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Whole blood
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Preparation method
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The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
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Reacting condition
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Overnight for assessment of the extent of COX-2 inhibition; 25 mins for assessment of the extent of COX-1 inhibition
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Applications
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In the assay for assessment of the extent of COX-2 inhibition, Valdecoxib inhibited lipopolysaccharide-induced PGE2 production, with an IC50 value of 0.89 μM. In the assay for assessment of the extent of COX-1 inhibition, Valdecoxib inhibited TXB2 production, with an IC50 value of 25.4 μM.
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Animal experiment [1]:
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Animal models
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Male SD rats
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Dosage form
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0.02, 0.032 or 10.2 mg/kg; p.o.
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Applications
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In SD rats, Valdecoxib inhibited carrageenan-induced foot pad edema, with an ED50 value of 10.2 mg/kg. In a rat adjuvant arthritis model, Valdecoxib also showed chronic anti-inflammatory activity, with an ED50 value of 0.032 mg/kg/day. In addition, Valdecoxib inhibited prostaglandin production at the inflammatory site in a carrageenan-induced air pouch model, with an ED50 value of 0.02 mg/kg.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Talley J J, Brown D L, Carter J S, et al. 4-[5-Methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. Journal of medicinal chemistry, 2000, 43(5): 775-777.
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