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Lipid Signaling: Cyclooxygenase (COX) Inhibitors  | | | Table 1: Selected Inhibitors I Inhibitors | Related Products
Cyclooxygenases (COX) are bifunctional hemoproteins that catalyze both the bisoxygenation of arachidonic acid to form PGG2 and the peroxidative reduction of PGG2 to form PGH2. Hence, COX has two different active sites. On one side, it has the cyclooxygenase active site, and on the opposite side is an entirely separate peroxidase site, which is required to activate the heme groups that participate in the cyclooxygenase reaction. The enzyme complex is a dimer of identical subunits, two cyclooxygenase active sites and two peroxidase active sites. COX-1 is a constitutive enzyme associated with the endoplasmic reticulum. It is responsible for maintaining normal physiologic function and is considered as a “housekeeping” enzyme. COX-2 is an inducible enzyme mainly associated with the nuclear envelope and is primarily associated with inflammation. Several cytokines and growth factors increase the expression of COX-2, mainly at inflammatory sites, producing prostaglandins, which mediate inflammation, pain, and fever. Increased expression of COX-2 has been associated with increased incidence of colon and breast cancers.
 Non-steroidal anti-inflammatory drugs (NSAIDs) exert antiinflammatory and analgesic effects through the inhibition of prostaglandin synthesis by blocking COX activity. Traditional NSAIDs inhibit prostaglandin formation through the inhibition of both COX-1 and COX-2. Inhibition of COX-1 is not necessary for antiinflammatory and analgesic effects but is thought to account for much of the toxicity of traditional NSAIDs. Based on structural differences in the active sites of these two isozymes, several new drugs have been developed that specifically inhibit only COX-2 activity. COX-2 selective inhibitors have the potential to provide the traditional benefits of NSAID with significantly reduced incidence of endoscopic ulcers. The selective COX-2 inhibitors have great clinical significance because they can allow the preservation of COX-1 activity, which is essential in maintaining prostaglandins that are important for normal platelet function and protection of the gastrointestinal mucosa, and still inhibit COX-2 to reduce inflammation and other pathologic processes. Due to the consideration of “inflammation as a factor” there has been an upsurge of interest in COX-2 inhibitors as possible candidates for the treatment of Alzheimer's disease. NSAIDs are believed to inhibit human Ab aggregation in vitro and reverse the b-sheet conformation of preformed fibrils. Several epidemiological studies have indeed shown that groups of people taking NSAIDs, for unrelated conditions, such as rheumatoid arthritis, have a reduced incidence of Alzheimer's disease. More recently, coxibs, highly selective COX-2 inhibitors, have been linked to abnormalities in vascular function and regulation of hemostatis/thrombosis. This has rekindled interest in several other COX-2 inhibitors for pain management.
| | | | Table 1: Selected Cyclooxygenase (COX) Inhibitors | | Product | Cat. No. | Comments | | COX-1 Inhibitor, FR122047 | | A cell-permeable trisubstituted thiazole compound that acts as a potent and selective inhibitor of COX-1 (IC50 = 28 nM and 65 mM for human recombinant COX-1 and COX-2, respectively). Displays ~2300-fold greater selectivity towards inhibition of COX-1 over COX-2. | | COX-2 Inhibitor I | | A selective inhibitor of COX-2 (IC50 = 650 nM) over COX-1 (IC50 > 10 mM). | | COX-2 Inhibitor II | | A cell-permeable isoxazolyl-benzenesulfonamide compound that acts as a potent and highly selective inhibitor of COX-2 both in vitro (IC50 = 4 nM for hCOX-2 vs. 114 mM for hCOX-1) and in vivo. | | Diclofenac, 4’-Hydroxy- | | A metabolite of Diclofenac that act as a potent inhibitor of COX-2 (IC50 = 16.9 nM). |
| | View complete table | | | | Inhibitors: Cyclooxygenase (COX) | |
| | | | Other Related Product | Product | | Comments | | Cyclooxygenase Inhibitor Set | | Provided as a 4 vial set. Each set contains 100 mg of Meloxicam (Cat. No. 444800), and 5 mg each of NS-398 (Cat. No. 349254), SC-560 (Cat. No. 565610), and Sulindac Sulfide (Cat. No. 574102). |
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