COX-1 | Cyclooxygenase | IUPHAR/BPS Guide to PHARMACOLOGY

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COX-1

target has curated data in GtoImmuPdb

Target id: 1375

Nomenclature: COX-1

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 - 599 9q32-q33.3 PTGS1 prostaglandin-endoperoxide synthase 1
Mouse - 602 2 24.19 cM Ptgs1 prostaglandin-endoperoxide synthase 1
Rat - 602 3 p11 Ptgs1 prostaglandin-endoperoxide synthase 1
Previous and Unofficial Names
COX1 | PGHS-1 | COX-1 | Cox-3 | cyclooxygenase 1 | cyclooxygenase 3 | PGH synthase 1 | prostaglandin G/H synthase 1 | prostaglandin G/H synthase and cyclooxygenase | prostaglandin H2 synthase 1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.14.99.1 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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
paracetamol Hs Inhibition 3.9 pKi 7
pKi 3.9 (Ki 1.136x10-4 M) [7]
(S)-ARN2508 Hs Inhibition 9.5 pIC50 18
pIC50 9.5 (IC50 2.9x10-10 M) [18]
FK-881 Hs Inhibition 8.3 pIC50 8
pIC50 8.3 (IC50 4.9x10-9 M) [8]
bromfenac Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.48x10-9 M) [1]
SC-560 Hs Inhibition 8.1 pIC50 23
pIC50 8.1 (IC50 9x10-9 M) [23]
diclofenac Hs Inhibition 7.9 pIC50 27
pIC50 7.9 (IC50 1.2x10-8 M) [27]
FR122047 Hs Inhibition 7.5 pIC50 19
pIC50 7.5 (IC50 3.16x10-8 M) [19]
meclofenamic acid Hs Inhibition 7.3 pIC50 10
pIC50 7.3 (IC50 5x10-8 M) [10]
flurbiprofen Hs Inhibition 7.1 pIC50 25
pIC50 7.1 (IC50 7.5x10-8 M) [25]
ketorolac Hs Inhibition 4.5 – 9.7 pIC50 24-25
pIC50 9.7 (IC50 1.9x10-10 M) [25]
pIC50 4.5 (IC50 3.15x10-5 M) [24]
Description: Instantaneous inhibition of human COX1 by compound (no pre-incubation).
fenoprofen Hs Inhibition 6.8 pIC50 1
pIC50 6.8 (IC50 1.45x10-7 M) [1]
indomethacin Hs Inhibition 6.6 pIC50 11
pIC50 6.6 (IC50 2.6x10-7 M) [11]
ketoprofen Hs Inhibition 6.5 pIC50 3
pIC50 6.5 (IC50 3.3x10-7 M) [3]
Description: Inhibition of COX1 in human whole blood.
suprofen Hs Inhibition 6.3 pIC50 3
pIC50 6.3 (IC50 5.6x10-7 M) [3]
sulindac Hs Inhibition 5.9 pIC50 26
pIC50 5.9 (IC50 1.2x10-6 M) [26]
SWE101 Hs Inhibition 5.9 pIC50 14
pIC50 5.9 (IC50 1.2x10-6 M) [14]
piroxicam Hs Inhibition 5.9 pIC50 16
pIC50 5.9 (IC50 1.3x10-6 M) [16]
oxaprozin Hs Inhibition 5.7 pIC50 12
pIC50 5.7 (IC50 2.2x10-6 M) [12]
ibuprofen Hs Inhibition 5.5 pIC50 9
pIC50 5.5 (IC50 3x10-6 M) [9]
phenylbutazone Hs Inhibition 5.5 pIC50 17
pIC50 5.5 (IC50 3x10-6 M) [17]
naproxen Hs Inhibition 5.5 pIC50 13
pIC50 5.5 (IC50 3.2x10-6 M) [13]
(R)-ARN2508 Hs Inhibition 5.4 pIC50 18
pIC50 5.4 (IC50 4x10-6 M) [18]
peptide 30 [PMID: 27019010] Hs Inhibition 5.2 pIC50 22
pIC50 5.2 (IC50 6x10-6 M) [22]
nimesulide Hs Inhibition 4.8 pIC50 20
pIC50 4.8 (IC50 1.74x10-5 M) [20]
SC-236 Hs Inhibition 4.8 pIC50 21
pIC50 4.8 (IC50 1.78x10-5 M) [21]
mefenamic acid Hs Inhibition 4.6 pIC50 6
pIC50 4.6 (IC50 2.5x10-5 M) [6]
meloxicam Hs Inhibition 4.4 pIC50 16
pIC50 4.4 (IC50 3.66x10-5 M) [16]
compound 9 [Kumar et al., 2019] Oa Inhibition 4.4 pIC50 15
pIC50 4.4 (IC50 3.992x10-5 M) [15]
Description: Inhibition of ovine COX1 using a proprietary COX inhibitor screening assay kit (Cayman chemical company).
GW406381 Hs Inhibition <4.1 pIC50 2
pIC50 <4.1 (IC50 >8.42x10-5 M) [2]
celecoxib Hs Inhibition 4.0 pIC50 11
pIC50 4.0 (IC50 1x10-4 M) [11]
compound 12a [PMID: 29031075] Hs Inhibition 4.0 pIC50 11
pIC50 4.0 (IC50 1.04x10-4 M) [11]
aspirin Hs Inhibition 3.3 pIC50 4
pIC50 3.3 (IC50 5.601x10-4 M) [4]
naproxcinod Hs Inhibition - - 5
[5]
View species-specific inhibitor tables
Inhibitor Comments
Piroxicam inhibits both cyclooxygenase isozymes [16], with maximum inhibition of PGE2 synthesis of approximately 60% for COX-2 and 35% for COX-1.
Fenoprofen is a non-selective COX inhibitor.
Immunopharmacology Comments
The cyclooxygenase enzymes are included in GtoImmuPdb as they are involved in the production of inflammatory mediators, and are long-standing anti-inflammatory drug targets.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnr1tm1Zim|Ptgs1tm1Unc Cnr1tm1Zim/Cnr1tm1Zim,Ptgs1tm1Unc/Ptgs1tm1Unc
involves: 129/Sv * 129P2/OlaHsd * C57BL/6J
MGI:104615  MGI:97797  MP:0002907 abnormal parturition PMID: 18833324 

References

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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, https://ntp.niehs.nih.gov/drugmatrix/index.html

2. Beswick P, Bingham S, Bountra C, Brown T, Browning K, Campbell I, Chessell I, Clayton N, Collins S, Corfield J et al.. (2004) Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett., 14 (21): 5445-8. [PMID:15454242]

3. 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]

4. Chowdhury MA, Abdellatif KR, Dong Y, Das D, Yu G, Velázquez CA, Suresh MR, Knaus EE. (2009) Synthesis and biological evaluation of salicylic acid and N-acetyl-2-carboxybenzenesulfonamide regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore: dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity. Bioorg. Med. Chem. Lett., 19 (24): 6855-61. [PMID:19884005]

5. Geusens P. (2009) Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD). Expert Opin Biol Ther, 9 (5): 649-57. [PMID:19392579]

6. Heinrich DM, Flanagan JU, Jamieson SM, Silva S, Rigoreau LJ, Trivier E, Raynham T, Turnbull AP, Denny WA. (2013) Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3. Eur J Med Chem, 62: 738-44. [PMID:23454516]

7. 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]

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. Janusz JM, Young PA, Scherz MW, Enzweiler K, Wu LI, Gan L, Pikul S, McDow-Dunham KL, Johnson CR, Senanayake CB et al.. (1998) New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations of the dihydrobenzofuran ring. J. Med. Chem., 41 (7): 1124-37. [PMID:9544212]

10. 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]

11. Kassab SE, Khedr MA, Ali HI, Abdalla MM. (2017) Discovery of new indomethacin-based analogs with potentially selective cyclooxygenase-2 inhibition and observed diminishing to PGE2 activities. Eur J Med Chem, 141: 306-321. [PMID:29031075]

12. 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]

13. 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]

14. Kramer JS, Woltersdorf S, Duflot T, Hiesinger K, Lillich FF, Knöll F, Wittmann SK, Klingler FM, Brunst S, Chaikuad A et al.. (2019) Discovery of the First in Vivo Active Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain. J. Med. Chem., 62 (18): 8443-8460. [PMID:31436984]

15. Kumar R, Saha N, Purohit P, Garg SK, Seth K, Meena VS, Dubey S, Dave K, Goyal R, Sharma SS et al.. (2019) Cyclic enaminone as new chemotype for selective cyclooxygenase-2 inhibitory, anti-inflammatory, and analgesic activities. European Journal of Medicinal Chemistry, In Press, Journal Pre-proof. DOI: 10.1016/j.ejmech.2019.111601

16. 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]

17. Look GC, Schullek JR, Holmes CP, Chinn JP, Gordon EM, Gallop MA. (1996) The identification of cyclooxygenase-1 inhibitors from 4-thiazolidinone combinatorial libraries. Bioorganic & Medicinal Chemistry Letters, 6 (6): 707-712.

18. Migliore M, Habrant D, Sasso O, Albani C, Bertozzi SM, Armirotti A, Piomelli D, Scarpelli R. (2016) Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies. Eur J Med Chem, 109: 216-37. [PMID:26774927]

19. 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]

20. 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]

21. 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]

22. Singh P, Kaur S, Kaur J, Singh G, Bhatti R. (2016) Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent. J. Med. Chem., 59 (8): 3920-34. [PMID:27019010]

23. 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. U.S.A., 95 (22): 13313-8. [PMID:9789085]

24. 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]

25. 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]

26. Zhou H, Liu W, Su Y, Wei Z, Liu J, Kolluri SK, Wu H, Cao Y, Chen J, Wu Y et al.. (2010) NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell, 17 (6): 560-73. [PMID:20541701]

27. 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]

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