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COX-1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1375

Nomenclature: COX-1

Family: Cyclooxygenase

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 599 9q33.2 PTGS1 prostaglandin-endoperoxide synthase 1
Mouse - 602 2 24.19 cM Ptgs1 prostaglandin-endoperoxide synthase 1
Rat - 602 3p11 Ptgs1 prostaglandin-endoperoxide synthase 1
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P23219 (Hs), P22437 (Mm), Q63921 (Rn)
BRENDA 1.14.99.1
CATH/Gene3D 1.10.640.10
ChEMBL Target CHEMBL221 (Hs), CHEMBL2649 (Mm), CHEMBL4042 (Rn)
DrugBank Target P23219 (Hs)
Ensembl Gene ENSG00000095303 (Hs), ENSMUSG00000047250 (Mm), ENSRNOG00000007415 (Rn)
Entrez Gene 5742 (Hs), 19224 (Mm), 24693 (Rn)
Human Protein Atlas ENSG00000095303 (Hs)
KEGG Enzyme 1.14.99.1
KEGG Gene hsa:5742 (Hs), mmu:19224 (Mm), rno:24693 (Rn)
OMIM 176805 (Hs)
Pharos P23219 (Hs)
UniProtKB P23219 (Hs), P22437 (Mm), Q63921 (Rn)
Wikipedia PTGS1 (Hs)
Enzyme Reaction Click here for help
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 go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
paracetamol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 3.9 pKi 7
⤷ pKi 3.9 (Ki 1.136x10-4 M) [7]
(S)-ARN2508 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.5 pIC50 18
⤷ pIC50 9.5 (IC50 2.9x10-10 M) [18]
FK-881 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 8
⤷ pIC50 8.3 (IC50 4.9x10-9 M) [8]
bromfenac Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 1
⤷ pIC50 8.1 (IC50 8.48x10-9 M) [1]
SC-560 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 23
⤷ pIC50 8.1 (IC50 9x10-9 M) [23]
diclofenac Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 27
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [27]
FR122047 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 19
⤷ pIC50 7.5 (IC50 3.16x10-8 M) [19]
meclofenamic acid Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 10
⤷ pIC50 7.3 (IC50 5x10-8 M) [10]
flurbiprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 25
⤷ pIC50 7.1 (IC50 7.5x10-8 M) [25]
ketorolac Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand 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 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 1
⤷ pIC50 6.8 (IC50 1.45x10-7 M) [1]
indomethacin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 11
⤷ pIC50 6.6 (IC50 2.6x10-7 M) [11]
ketoprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 3
⤷ pIC50 6.5 (IC50 3.3x10-7 M) [3]
Description: Inhibition of COX1 in human whole blood.
suprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 3
⤷ pIC50 6.3 (IC50 5.6x10-7 M) [3]
sulindac Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 26
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [26]
SWE101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 14
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [14]
piroxicam Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 16
⤷ pIC50 5.9 (IC50 1.3x10-6 M) [16]
oxaprozin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.7 pIC50 12
⤷ pIC50 5.7 (IC50 2.2x10-6 M) [12]
ibuprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 9
⤷ pIC50 5.5 (IC50 3x10-6 M) [9]
phenylbutazone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 17
⤷ pIC50 5.5 (IC50 3x10-6 M) [17]
naproxen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 13
⤷ pIC50 5.5 (IC50 3.2x10-6 M) [13]
(R)-ARN2508 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.4 pIC50 18
⤷ pIC50 5.4 (IC50 4x10-6 M) [18]
peptide 30 [PMID: 27019010] Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.2 pIC50 22
⤷ pIC50 5.2 (IC50 6x10-6 M) [22]
nimesulide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.8 pIC50 20
⤷ pIC50 4.8 (IC50 1.74x10-5 M) [20]
SC-236 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.8 pIC50 21
⤷ pIC50 4.8 (IC50 1.78x10-5 M) [21]
pIC50 4.8 (IC50 1.78x10-5 M) [21]
mefenamic acid Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.6 pIC50 6
⤷ pIC50 4.6 (IC50 2.5x10-5 M) [6]
meloxicam Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.4 pIC50 16
⤷ pIC50 4.4 (IC50 3.66x10-5 M) [16]
celecoxib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 4.0 – 4.8 pIC50 11,21
⤷ pIC50 4.0 – 4.8 (IC50 1x10-4 – 1.5x10-5 M) [11,21]
compound 9 [Kumar et al., 2019] Small molecule or natural product Immunopharmacology Ligand 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 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <4.1 pIC50 2
⤷ pIC50 <4.1 (IC50 >8.42x10-5 M) [2]
compound 12a [PMID: 29031075] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 4.0 pIC50 11
⤷ pIC50 4.0 (IC50 1.04x10-4 M) [11]
aspirin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 3.3 pIC50 4
⤷ pIC50 3.3 (IC50 5.601x10-4 M) [4]
naproxcinod Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand 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
Phenotypes, Alleles and Disease Models Click here for help 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. Eur J Med Chem, 182: 111601. DOI: 10.1016/j.ejmech.2019.111601 [PMID:31445233]

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. Bioorg Med Chem Lett, 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 USA, 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 USA, 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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