Prostaglandin (PG) G/H synthase, most commonly referred to as cyclooxygenase (COX, (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor : oxygen oxidoreductase) activity, catalyses the formation of PGG₂ from arachidonic acid. Hydroperoxidase activity inherent in the enzyme catalyses the formation of PGH₂ from PGG₂. COX-1 and -2 can be nonselectively inhibited by ibuprofen, ketoprofen, naproxen, indomethacin and paracetamol (acetaminophen). PGH₂ may then be metabolised to prostaglandins and thromboxanes by various prostaglandin synthases in an apparently tissue-dependent manner.

1. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

2. Bayly CI, Black WC, Léger S, Ouimet N, Ouellet M, Percival MD. (1999) Structure-based design of COX-2 selectivity into flurbiprofen. Bioorg. Med. Chem. Lett., 9 (3): 307-12. [PMID:10091674]

3. Black WC, Brideau C, Chan CC, Charleson S, Cromlish W, Gordon R, Grimm EL, Hughes G, Leger S, Li CS et al.. (2003) 3,4-Diaryl-5-hydroxyfuranones: highly selective inhibitors of cyclooxygenase-2 with aqueous solubility. Bioorg. Med. Chem. Lett., 13 (6): 1195-8. [PMID:12643942]

4. Blobaum AL, Marnett LJ. (2007) Molecular determinants for the selective inhibition of cyclooxygenase-2 by lumiracoxib. J. Biol. Chem., 282 (22): 16379-90. [PMID:17434872]

5. Blobaum AL, Marnett LJ. (2007) Structural and functional basis of cyclooxygenase inhibition. J. Med. Chem., 50 (7): 1425-41. [PMID:17341061]

6. Bézière N, Goossens L, Pommery J, Vezin H, Touati N, Hénichart JP, Pommery N. (2008) New NSAIDs-NO hybrid molecules with antiproliferative properties on human prostatic cancer cell lines. Bioorg. Med. Chem. Lett., 18 (16): 4655-7. [PMID:18667313]

7. Hieke M, Ness J, Steri R, Greiner C, Werz O, Schubert-Zsilavecz M, Weggen S, Zettl H. (2011) SAR studies of acidic dual γ-secretase/PPARγ modulators. Bioorg. Med. Chem., 19 (18): 5372-82. [PMID:21873070]

8. Kalgutkar AS, Rowlinson SW, Crews BC, Marnett LJ. (2002) Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett., 12 (4): 521-4. [PMID:11844663]

9. Lazer ES, Miao CK, Cywin CL, Sorcek R, Wong HC, Meng Z, Potocki I, Hoermann M, Snow RJ, Tschantz MA et al.. (1997) Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity. J. Med. Chem., 40 (6): 980-9. [PMID:9083488]

10. Ochi T, Motoyama Y, Goto T. (2000) The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models. Eur. J. Pharmacol., 391 (1-2): 49-54. [PMID:10720634]

11. Ottanà R, Carotti S, Maccari R, Landini I, Chiricosta G, Caciagli B, Vigorita MG, Mini E. (2005) In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I. Bioorg. Med. Chem. Lett., 15 (17): 3930-3. [PMID:15993594]

12. Riendeau D, Percival MD, Brideau C, Charleson S, Dubé D, Ethier D, Falgueyret JP, Friesen RW, Gordon R, Greig G et al.. (2001) Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J. Pharmacol. Exp. Ther., 296 (2): 558-66. [PMID:11160644]

13. Talley JJ, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Perkins WE, Rogers RS, Shaffer AF, Zhang YY et al.. (2000) 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J. Med. Chem., 43 (5): 775-7. [PMID:10715145]

14. Viegas A, Manso J, Corvo MC, Marques MM, Cabrita EJ. (2011) Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR. J. Med. Chem., 54 (24): 8555-62. [PMID:22091869]

15. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. (1999) Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc. Natl. Acad. Sci. U.S.A., 96 (13): 7563-8. [PMID:10377455]

16. Zou J, Jin D, Chen W, Wang J, Liu Q, Zhu X, Zhao W. (2005) Selective cyclooxygenase-2 inhibitors from Calophyllum membranaceum. J. Nat. Prod., 68 (10): 1514-8. [PMID:16252917]

Subcommittee members: Jane A. Mitchell (Chairperson) Head of Cardiothoracic Pharmacology, Cardiothoracic Pharmacology, Head of Vascular Biology Section, National Heart and Lung Institute, Institute of Cardiovascular Medicine & Science, Dovehouse Street, Imperial College, London SW3 6LY