Cyclooxygenase celecoxib

The efficacy and safety of cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) have not been fully assessed in gouty arthritis, but they are more costly than conventional NSAIDs and are unlikely to result in fewer GI complications because of the short duration of therapy. 

The lability of benzylic positions to cytochrome P450 metabolism has been exploited to decrease the unacceptably low clearance and resultant long half-life of various compounds. For example celecoxib, a selective cyclooxygenase inhibitor, has a half-life of 3.5 h in the rat. Early structural leads, represented by compoimds in... 

Outlook Cyclooxygenase (COX) has two isozymes COX-1, a constitutive form present in stomach and kidney and COX-2, which is induced in inflammatory cells in response to appropriate stimuli. Presently available NSAIDs inhibit both isozymes. The search for COX-2-selective agents (Celecoxib, Ro-fecoxib) is intensifying because, in theory, these ought to be tolerated better. 

Steinbach G, Lynch P, Phillips R, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000 29 1946-1952. 

Jacoby RF, Seibert K, Cole CE, et al. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 2000 60 5040-5044. 

Kawamori T, Rao CV, Seibert K, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998 58 409-412. 

Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 2000 275 11,397-11,403. 

Leese PT, Hubbard RC, Karim A, et al. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults a randomized, controlled trial. J Clin Pharmacol 2000 40 124—132. 

S. M. Fischer, H.-H. Lo, G.B. Gordon, K. Seibert, G. Kelloff, R.A. Lubet, C.J. Conti, Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol. Carcinog. 25 (1999) 231. 

Chapter 2. Anti-inflammatory Cyclooxygenase-2 Selective Inhibitors Celecoxib (Celebrex ) and Rofecoxib (Vioxx )... 

Table 1. Cyclooxygenase inhibitory activities of celecoxib (1), rofecoxib (2) and indomethacin (4), IC50 (pM).

Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis, Am. J. Gastroenterol. 2001, 96, 1019-1027. 

An optimization of the two classical principles mentioned above was achieved by the generation of more selective compounds. For example, the cyclooxygenase-2- (COX-2) selective NSAIDS (Celecoxib, Rofecoxib) with improved gastric tolerance have entered the market with tremendous success (see Chapter 2). In addition,... 

Cyclooxygenase type 2 [COX-2] inhibitors -coxib Celecoxib Pain, inflammation (15)... 

Orengo, I.F., Gerguis, J., Phillips, R., Guevara, A., Lewis, A.T., and Black, H.S., Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer a study in the hairless mouse model, Arch. Dermatol., 138, 751, 2002. 

The major problem of NSAIDs is gastrointestinal (GI) irritation, leading to ulceration. Recent drugs such as celecoxib (a cyclooxygenase-II inhibitor) have a mild effect on the GI tract and have proven to be the drugs of choice for the treatment of rheumatoid arthritis. 

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