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.

* Key recommended reading is highlighted with an asterisk

* Mitchell JA, Kirkby NS, Ahmetaj-Shala B, Armstrong PC, Crescente M, Ferreira P, Lopes Pires ME, Vaja R, Warner TD. (2021) Cyclooxygenases and the cardiovascular system. Pharmacol Ther, 217: 107624. [PMID:32640277]

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. 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]

6. Gierse JK, McDonald JJ, Hauser SD, Rangwala SH, Koboldt CM, Seibert K. (1996) A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. J Biol Chem, 271 (26): 15810-4. [PMID:8663121]

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. Imanishi J, Morita Y, Yoshimi E, Kuroda K, Masunaga T, Yamagami K, Kuno M, Hamachi E, Aoki S, Takahashi F et al.. (2011) Pharmacological profile of FK881(ASP6537), a novel potent and selective cyclooxygenase-1 inhibitor. Biochem Pharmacol, 82 (7): 746-54. [PMID:21745460]

9. 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]

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. Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM et al.. (1997) Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). J Med Chem, 40 (9): 1347-65. [PMID:9135032]

13. Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, Talley JJ, Masferrer JL, Seibert K, Isakson PC. (1998) Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA, 95 (22): 13313-8. [PMID:9789085]

14. 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]

15. 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]

16. 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 USA, 96 (13): 7563-8. [PMID:10377455]

17. 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 UK

Other contributors: Angelo A. Izzo Department of Pharmacy School of Medicine and Surgery University of Naples Federico II Naples, Italy