Target id: 1376

Nomenclature: COX-2

Family: Cyclooxygenase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 604 1q25.2-q25.3 PTGS2 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Mouse - 604 1 63.84 cM Ptgs2 prostaglandin-endoperoxide synthase 2
Rat - 604 13q21 Ptgs2 prostaglandin-endoperoxide synthase 2
Previous and Unofficial Names
cyclooxygenase 2
PGH synthase 2
prostaglandin G/H synthase 2
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Reference Database
KEGG Enzyme
Enzyme Reaction
EC Number: Hydrogen donor + arachidonic acid + 2O2 = hydrogen acceptor + H2O + PGH2
Description Reaction Reference
Arachidonic acid => PGG2 => PGH2
This enzyme is also associated with the following reaction: Docosahexaenoic acid => PGH3

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
lumiracoxib Hs Inhibition 6.5 pKi 4
pKi 6.5 (Ki 3.2x10-7 M) [4]
paracetamol Hs Inhibition 4.6 pKi 10
pKi 4.6 (Ki 2.58x10-5 M) [10]
celecoxib Hs Inhibition 8.7 pIC50 3
pIC50 8.7 (IC50 2x10-9 M) [3]
benzquinamide Hs Inhibition 8.3 pIC50 1
pIC50 8.3 (IC50 4.8x10-9 M) [1]
valdecoxib Hs Inhibition 8.3 pIC50 19
pIC50 8.3 (IC50 5x10-9 M) [19]
flurbiprofen Hs Inhibition 8.0 pIC50 2
pIC50 8.0 (IC50 1x10-8 M) [2]
diclofenac Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 2x10-8 M) [5]
meclofenamic acid Hs Inhibition 7.4 pIC50 11
pIC50 7.4 (IC50 4x10-8 M) [11]
carprofen Hs Inhibition 7.0 pIC50 9
pIC50 7.0 (IC50 1.02x10-7 M) [9]
Description: Inhibition of COX-2-induced conversion of arachadonic acid to 12-HHT.
meloxicam Hs Inhibition 6.3 pIC50 15
pIC50 6.3 (IC50 4.9x10-7 M) [15]
rofecoxib Hs Inhibition 6.1 – 6.5 pIC50 21
pIC50 6.1 – 6.5 [21]
nimesulide Hs Inhibition 6.2 pIC50 16
pIC50 6.2 (IC50 6x10-7 M) [16]
ketoprofen Hs Inhibition 6.2 pIC50 6
pIC50 6.2 (IC50 6.9x10-7 M) [6]
Description: Inhibition of COX2 in human whole blood.
etoricoxib Hs Inhibition 6.0 pIC50 17
pIC50 6.0 (IC50 1.1x10-6 M) [17]
ibuprofen Hs Inhibition 5.9 pIC50 20
pIC50 5.9 (IC50 1.35x10-6 M) [20]
aspirin Hs Inhibition 5.6 pIC50 18
pIC50 5.6 (IC50 2.4x10-6 M) [18]
naproxen Hs Inhibition 5.6 pIC50 14
pIC50 5.6 (IC50 2.5x10-6 M) [14]
ketorolac Hs Inhibition 4.2 – 6.9 pIC50 20
pIC50 6.9 (IC50 1.2x10-7 M) [20]
Description: Inhibition of human COX2 measured after pre-incubation of enzyme with compound.
pIC50 4.2 (IC50 6.05x10-5 M) [20]
Description: Instantaneous inhibition of human COX2 by compound (no pre-incubation).
suprofen Hs Inhibition 5.6 pIC50 6
pIC50 5.6 (IC50 2.75x10-6 M) [6]
mefenamic acid Hs Inhibition 5.5 pIC50 7
pIC50 5.5 (IC50 2.9x10-6 M) [7]
oxaprozin Hs Inhibition 4.4 pIC50 13
pIC50 4.4 (IC50 3.6x10-5 M) [13]
etodolac Hs Inhibition 4.3 pIC50 12
pIC50 4.3 (IC50 5.3x10-5 M) [12]
Description: Measured as LPS-induced PGE2 production in COX-1-inhibited human monocytes.
piroxicam Hs Inhibition 3.7 pIC50 22
pIC50 3.7 (IC50 2.18x10-4 M) [22]
phenylbutazone Hs Inhibition 3.5 pIC50 22
pIC50 3.5 (IC50 2.84x10-4 M) [22]
Inhibitor Comments
Carprofen is a COX-2 selective cyclooxygenase inhibitor, at least when comparing human COX-2 vs. ovine COX-1 in the same assay [8-9].
The data for etodolac in the table above is from Kato et al. (2001) [12]. In the same study etodolac's IC50 for COX-1 was reported to be >100 μM.
Piroxicam inhibits both cyclooxygenase isozymes [15], with maximum inhibition of PGE2 synthesis of approximately 60% for COX-2 and 35% for COX-1. Ketorolac is also a non-selective COX inhibitor.


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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,

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]

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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]

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9. 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]

10. Hinz B, Cheremina O, Brune K. (2008) Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J.22 (2): 383-90. [PMID:17884974]

11. 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]

12. Kato M, Nishida S, Kitasato H, Sakata N, Kawai S. (2001) Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes. J. Pharm. Pharmacol.53 (12): 1679-85. [PMID:11804398]

13. Kawai S, Nishida S, Kato M, Furumaya Y, Okamoto R, Koshino T, Mizushima Y. (1998) Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells. Eur. J. Pharmacol.347 (1): 87-94. [PMID:9650852]

14. Kolasa T, Brooks CD, Rodriques KE, Summers JB, Dellaria JF, Hulkower KI, Bouska J, Bell RL, Carter GW. (1997) Nonsteroidal anti-inflammatory drugs as scaffolds for the design of 5-lipoxygenase inhibitors. J. Med. Chem.40 (5): 819-24. [PMID:9057869]

15. 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]

16. 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]

17. 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]

18. Takahashi T, Miyazawa M. (2012) N-Caffeoyl serotonin as selective COX-2 inhibitor. Bioorg. Med. Chem. Lett.22 (7): 2494-6. [PMID:22386242]

19. 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]

20. 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]

21. 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]

22. Wilkerson WW, Copeland RA, Covington M, Trzaskos JM. (1995) Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition. J. Med. Chem.38 (20): 3895-901. [PMID:7562922]

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Cyclooxygenase: COX-2 . Last modified on 16/07/2015. Accessed on 28/08/2015. IUPHAR/BPS Guide to PHARMACOLOGY,