product name Valdecoxib
Description: Valdecoxib is a potent and selective inhibitor of COX-2 with IC50 of 5 nM. Valdecoxib is developed for the treatment 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.
References: J Med Chem. 2000 Mar 9;43(5):775-7; J Pharmacol Exp Ther. 2005 Mar;312(3):1206-12.
314.36
Formula
C16H14N2O3S
CAS No.
181695-72-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 63 mg/mL (200.4 mM)
Water: <1 mg/mL
Ethanol: 18 mg/mL (57.2 mM)
Solubility (In vivo)
0.5% methylcellulose+0.2% Tween 80: 19 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19408911
| In Vitro |
In vitro activity: Valdecoxib inhibits LPS-induced PGE2 production in plasma with IC50 of 0.89 μM for assessment of the extent of COX-2 inhibition. Valdecoxib inhibits TxB2 production in plasma with IC50 of 25.4 μM for assessment of the extent of COX-1 inhibition. Valdecoxib binds to COX-2 with Ka of 1.1×105 M/s. The overall saturation binding affinity for COX-2 of Valdecoxib is 2.6 nM. Valdecoxib shows similar activity in the human whole-blood COX assay (COX-2 IC50 = 0.24 μM; COX-1 IC50 = 21.9 μM). The affinity of [3H]Valdecoxib for COX-2 with KD of 3.2 nM. The binding of Valdecoxib to COX-2 seems to be both rapid and slowly reversible with association rates of 4.5 × 106/M/min and dissociation rates of 7.0 × 10-3/min (t1/2 of 98 min). The percent of dissolved Valdecoxib at 15 min (DP15) is 10.5% for Valdecoxib and 50%, 91% and 93% for its hydrophilic derivatives (VALD-βCd, VALD-HPβCd and VALD-SBE7βCd complexes), respectively. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Valdecoxib administrated orally inhibits rat carrageenan foot pad edema with ED50 of 10.2 mg/kg. Valdecoxib administrated orally shows chronic antiinflammatory activity with ED50 of 0.032 mg/kg/day in rat adjuvant arthritis model. Valdecoxib administrated orally shows blockade of prostaglandin production at the inflammatory site with ED50 of 0.02 mg/kg in the rat carrageenan air pouch model. Valdecoxib demonstrates marked potency in acute and chronic models of inflammation (air pouch ED50 = 0.06 mg/kg; paw edema ED50 = 5.9 mg/kg; adjuvant arthritis ED50 = 0.03 mg/kg) in rats. Valdecoxib alone shows slow in vivo absorption giving maximum % inhibition of edema (16%) after a period of 3 hour. In contrast, VALD-βCd and VALD-SBE7βCd complexes shows high absorption rate in vivo achieving more than 50% inhibition of edema in the 1 hour and maximum percentage of inhibition of edema (66%) after a period of 3 hours. Valdecoxib (5 mg/kg, po) results in AUC in plasma of 3.58 μg*h/mL and 2.08 μg*h/mL in males and female mice, respectively. Valdecoxib (5 mg/kg, po) results in AUC red blood cells of 12.1 μg*h/mL and 6.42 μg*h/mL in males and female mice, respectively. |
| Animal model | Male Sprague-Dawley rats |
| Formulation & Dosage | Formulated in 0.5% methyl cellulose and 0.025% Tween-20; 10.2 mg/kg; Oral gavage |
| References | J Med Chem. 2000 Mar 9;43(5):775-7; J Pharmacol Exp Ther. 2005 Mar;312(3):1206-12. |
