COX-1

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

   GtoImmuPdb view: OFF :     COX-1 has curated GtoImmuPdb data

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 | cyclooxygenase 1 | COX-1 | Cox-3 | 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
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
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 Affinity Units Reference
paracetamol Hs Inhibition 3.9 pKi 6
pKi 3.9 (Ki 1.136x10-4 M) [6]
(S)-ARN2508 Hs Inhibition 9.5 pIC50 13
pIC50 9.5 (IC50 2.9x10-10 M) [13]
bromfenac Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.48x10-9 M) [1]
diclofenac Hs Inhibition 7.9 pIC50 19
pIC50 7.9 (IC50 1.2x10-8 M) [19]
FR122047 Hs Inhibition 7.5 pIC50 14
pIC50 7.5 (IC50 3.16x10-8 M) [14]
meclofenamic acid Hs Inhibition 7.3 pIC50 8
pIC50 7.3 (IC50 5x10-8 M) [8]
flurbiprofen Hs Inhibition 7.1 pIC50 18
pIC50 7.1 (IC50 7.5x10-8 M) [18]
ketorolac Hs Inhibition 4.5 – 9.7 pIC50 17-18
pIC50 9.7 (IC50 1.9x10-10 M) [18]
pIC50 4.5 (IC50 3.15x10-5 M) [17]
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]
ketoprofen Hs Inhibition 6.5 pIC50 2
pIC50 6.5 (IC50 3.3x10-7 M) [2]
Description: Inhibition of COX1 in human whole blood.
suprofen Hs Inhibition 6.3 pIC50 2
pIC50 6.3 (IC50 5.6x10-7 M) [2]
piroxicam Hs Inhibition 5.9 pIC50 11
pIC50 5.9 (IC50 1.3x10-6 M) [11]
oxaprozin Hs Inhibition 5.7 pIC50 9
pIC50 5.7 (IC50 2.2x10-6 M) [9]
ibuprofen Hs Inhibition 5.5 pIC50 7
pIC50 5.5 (IC50 3x10-6 M) [7]
phenylbutazone Hs Inhibition 5.5 pIC50 12
pIC50 5.5 (IC50 3x10-6 M) [12]
naproxen Hs Inhibition 5.5 pIC50 10
pIC50 5.5 (IC50 3.2x10-6 M) [10]
(R)-ARN2508 Hs Inhibition 5.4 pIC50 13
pIC50 5.4 (IC50 4x10-6 M) [13]
peptide 30 [PMID: 27019010 ] Hs Inhibition 5.2 pIC50 16
pIC50 5.2 (IC50 6x10-6 M) [16]
nimesulide Hs Inhibition 4.8 pIC50 15
pIC50 4.8 (IC50 1.74x10-5 M) [15]
mefenamic acid Hs Inhibition 4.6 pIC50 5
pIC50 4.6 (IC50 2.5x10-5 M) [5]
meloxicam Hs Inhibition 4.4 pIC50 11
pIC50 4.4 (IC50 3.66x10-5 M) [11]
aspirin Hs Inhibition 3.3 pIC50 3
pIC50 3.3 (IC50 5.601x10-4 M) [3]
naproxcinod Hs Inhibition - - 4
[4]
Inhibitor Comments
Piroxicam inhibits both cyclooxygenase isozymes [11], 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
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  inflammatory response (GO:0006954) IEA
References: 
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. 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]

3. 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]

4. Geusens P. (2009) Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD). Expert Opin Biol Ther9 (5): 649-57. [PMID:19392579]

5. 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 Chem62: 738-44. [PMID:23454516]

6. 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]

7. 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]

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. 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]

10. 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]

11. 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]

12. 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 Letters6 (6): 707-712.

13. Migliore M, Habrant D, Sasso O, Albani C, Bertozzi SM, Armirotti A, Piomelli D, Scarpelli R. (2015) Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies. Eur J Med Chem109: 216-237 [Epub ahead of print]. [PMID:26774927]

14. 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]

15. 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]

16. 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]

17. 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]

18. 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]

19. 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]

How to cite this page

Cyclooxygenase: COX-1 . Last modified on 21/04/2017. Accessed on 17/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1375.