COX-2 | Cyclooxygenase | IUPHAR/BPS Guide to PHARMACOLOGY

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target has curated data in GtoImmuPdb

Target id: 1376

Nomenclature: COX-2

Family: Cyclooxygenase

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 604 1q31.1 PTGS2 prostaglandin-endoperoxide synthase 2
Mouse - 604 1 63.84 cM Ptgs2 prostaglandin-endoperoxide synthase 2
Rat - 604 13q21 Ptgs2 prostaglandin-endoperoxide synthase 2
Previous and Unofficial Names
PTGS2 | COX2 | cyclooxygenase 2 | PGH synthase 2 | PGHS-2 | prostaglandin G/H synthase 2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of arachidonic acid bound to the cyclooxygenase active site of COX2.
Ligand:  arachidonic acid
Resolution:  2.4Å
Species:  Mouse
References:  22
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of murine cycloxygenase in complex with a harmaline analog, 4,9-dihydro-3H-pyrido[3,4-b]indole
PDB Id:  6V3R
Ligand:  compound 3 [Uddin et al., 2020]
Resolution:  2.66Å
Species:  Mouse
References:  35
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 Value Parameter Reference
SC-236 Hs Inhibition 8.0 pIC50 29
pIC50 8.0 (IC50 1x10-8 M) [29]
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
lumiracoxib Hs Inhibition 6.5 pKi 6
pKi 6.5 (Ki 3.2x10-7 M) [6]
paracetamol Hs Inhibition 4.6 pKi 14
pKi 4.6 (Ki 2.58x10-5 M) [14]
NS-398 Hs Inhibition 8.7 pIC50 17
pIC50 8.7 (IC50 1.9x10-9 M) [17]
Description: Measuring inhibition of PGE2 production in human IL-1-stimulated synovial cells
GW406381 Hs Inhibition 8.5 pIC50 4
pIC50 8.5 (IC50 3x10-9 M) [4]
benzquinamide Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 4.8x10-9 M) [2]
valdecoxib Hs Inhibition 8.3 pIC50 34
pIC50 8.3 (IC50 5x10-9 M) [34]
flurbiprofen Hs Inhibition 8.0 pIC50 3
pIC50 8.0 (IC50 1x10-8 M) [3]
(S)-ARN2508 Hs Inhibition 7.9 pIC50 27
pIC50 7.9 (IC50 1.2x10-8 M) [27]
diclofenac Hs Inhibition 7.7 pIC50 7
pIC50 7.7 (IC50 2x10-8 M) [7]
celecoxib Hs Inhibition 6.5 – 8.7 pIC50 5,19
pIC50 8.7 (IC50 2x10-9 M) [5]
pIC50 6.5 (IC50 3x10-7 M) [19]
meclofenamic acid Hs Inhibition 7.4 pIC50 18
pIC50 7.4 (IC50 4x10-8 M) [18]
peptide 30 [PMID: 27019010] Hs Inhibition 7.2 pIC50 31
pIC50 7.2 (IC50 6x10-8 M) [31]
carprofen Hs Inhibition 7.0 pIC50 13
pIC50 7.0 (IC50 1.02x10-7 M) [13]
Description: Inhibition of COX-2-induced conversion of arachadonic acid to 12-HHT.
compound 3 [Uddin et al., 2020] Mm Inhibition 6.7 pIC50 35
pIC50 6.7 (IC50 2x10-7 M) [35]
Description: Biochemical assay measuring inhibiton of purified murine COX-2.
compound 12a [PMID: 29031075] Hs Inhibition 6.6 pIC50 19
pIC50 6.6 (IC50 2.3x10-7 M) [19]
compound 9 [Kumar et al., 2019] Hs Inhibition 6.4 pIC50 25
pIC50 6.4 (IC50 3.67x10-7 M) [25]
Description: Inhibition of recombinant hCOX2 in vitro.
SWE101 Hs Inhibition 6.4 pIC50 24
pIC50 6.4 (IC50 4.2x10-7 M) [24]
meloxicam Hs Inhibition 6.3 pIC50 26
pIC50 6.3 (IC50 4.9x10-7 M) [26]
rofecoxib Hs Inhibition 6.1 – 6.5 pIC50 37
pIC50 6.1 – 6.5 [37]
nimesulide Hs Inhibition 6.2 pIC50 28
pIC50 6.2 (IC50 6x10-7 M) [28]
ketoprofen Hs Inhibition 6.2 pIC50 8
pIC50 6.2 (IC50 6.9x10-7 M) [8]
Description: Inhibition of COX2 in human whole blood.
resveratrol Hs Inhibition 6.1 pIC50 15
pIC50 6.1 (IC50 7.5x10-7 M) [15]
esflurbiprofen Hs Inhibition 6.0 pIC50 9
pIC50 6.0 (IC50 9.1x10-7 M) [9]
Description: Inhibition of COX-2 in human blood.
etoricoxib Hs Inhibition 6.0 pIC50 30
pIC50 6.0 (IC50 1.1x10-6 M) [30]
ibuprofen Hs Inhibition 5.9 pIC50 36
pIC50 5.9 (IC50 1.35x10-6 M) [36]
aspirin Hs Inhibition 5.6 pIC50 33
pIC50 5.6 (IC50 2.4x10-6 M) [33]
naproxen Hs Inhibition 5.6 pIC50 23
pIC50 5.6 (IC50 2.5x10-6 M) [23]
indomethacin Hs Inhibition 5.6 pIC50 19
pIC50 5.6 (IC50 2.63x10-6 M) [19]
ketorolac Hs Inhibition 4.2 – 6.9 pIC50 36
pIC50 6.9 (IC50 1.2x10-7 M) [36]
Description: Inhibition of human COX2 measured after pre-incubation of enzyme with compound.
pIC50 4.2 (IC50 6.05x10-5 M) [36]
Description: Instantaneous inhibition of human COX2 by compound (no pre-incubation).
suprofen Hs Inhibition 5.6 pIC50 8
pIC50 5.6 (IC50 2.75x10-6 M) [8]
mefenamic acid Hs Inhibition 5.5 pIC50 11
pIC50 5.5 (IC50 2.9x10-6 M) [11]
FK-881 Hs Inhibition 5.5 pIC50 16
pIC50 5.5 (IC50 3.2x10-6 M) [16]
sulindac Hs Inhibition 5.5 pIC50 39
pIC50 5.5 (IC50 3.4x10-6 M) [39]
SC-560 Hs Inhibition 5.2 pIC50 32
pIC50 5.2 (IC50 6.3x10-6 M) [32]
(R)-ARN2508 Hs Inhibition 4.6 pIC50 27
pIC50 4.6 (IC50 2.28x10-5 M) [27]
oxaprozin Hs Inhibition 4.4 pIC50 21
pIC50 4.4 (IC50 3.6x10-5 M) [21]
etodolac Hs Inhibition 4.3 pIC50 20
pIC50 4.3 (IC50 5.3x10-5 M) [20]
Description: Measured as LPS-induced PGE2 production in COX-1-inhibited human monocytes.
piroxicam Hs Inhibition 3.7 pIC50 38
pIC50 3.7 (IC50 2.18x10-4 M) [38]
phenylbutazone Hs Inhibition 3.5 pIC50 38
pIC50 3.5 (IC50 2.84x10-4 M) [38]
naproxcinod Hs Inhibition - - 10
View species-specific inhibitor tables
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 [12-13].
The data for etodolac in the table above is from Kato et al. (2001) [20]. In the same study etodolac's IC50 for COX-1 was reported to be >100 μM.
Piroxicam inhibits both cyclooxygenase isozymes [26], 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.
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. The role of COX-2 in immuno-oncology is reviewed in [1].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0031622 positive regulation of fever generation ISS
GO:0050727 regulation of inflammatory response NAS
GO:0150077 regulation of neuroinflammatory response ISS
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0031622 positive regulation of fever generation ISS
GO:0050727 regulation of inflammatory response NAS
GO:0150077 regulation of neuroinflammatory response ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 7 GO processes
GO:0010575 positive regulation of vascular endothelial growth factor production ISS
GO:0019221 cytokine-mediated signaling pathway TAS
GO:0034097 response to cytokine ISO
GO:0071636 positive regulation of transforming growth factor beta production ISS
GO:0090271 positive regulation of fibroblast growth factor production ISS
GO:0090362 positive regulation of platelet-derived growth factor production ISS
click arrow to show/hide IEA associations
GO:0034612 response to tumor necrosis factor IEA


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