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COX-2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1376

Nomenclature: COX-2

Family: Cyclooxygenase

Contents:

Gene and Protein Information Click here for help
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 Click here for help
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 Click here for help
Alphafold P35354 (Hs), Q05769 (Mm), P35355 (Rn)
BRENDA 1.14.99.1
CATH/Gene3D 1.10.640.10
ChEMBL Target CHEMBL230 (Hs), CHEMBL4321 (Mm), CHEMBL2977 (Rn)
DrugBank Target P35354 (Hs)
Ensembl Gene ENSG00000073756 (Hs), ENSMUSG00000032487 (Mm), ENSRNOG00000002525 (Rn)
Entrez Gene 5743 (Hs), 19225 (Mm), 29527 (Rn)
Human Protein Atlas ENSG00000073756 (Hs)
KEGG Enzyme 1.14.99.1
KEGG Gene hsa:5743 (Hs), mmu:19225 (Mm), rno:29527 (Rn)
OMIM 600262 (Hs)
Pharos P35354 (Hs)
SynPHARM 79412 (in complex with meclofenamic acid)
79499 (in complex with mefenamic acid)
UniProtKB P35354 (Hs), Q05769 (Mm), P35355 (Rn)
Wikipedia PTGS2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of arachidonic acid bound to the cyclooxygenase active site of COX2.
PDB Id:  1CVU
Ligand:  arachidonic acid
Resolution:  2.4Å
Species:  Mouse
References:  23
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:  37
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
lumiracoxib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.5 pKi 6
⤷ pKi 6.5 (Ki 3.2x10-7 M) [6]
paracetamol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.6 pKi 15
⤷ pKi 4.6 (Ki 2.58x10-5 M) [15]
NS-398 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 18
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [18]
Description: Measuring inhibition of PGE2 production in human IL-1-stimulated synovial cells
GW406381 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 4
⤷ pIC50 8.5 (IC50 3x10-9 M) [4]
benzquinamide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 2
⤷ pIC50 8.3 (IC50 4.8x10-9 M) [2]
valdecoxib 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 8.3 pIC50 36
⤷ pIC50 8.3 (IC50 5x10-9 M) [36]
SC-236 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.0 – 8.3 pIC50 11,30
⤷ pIC50 8.0 – 8.3 (IC50 1x10-8 – 5x10-9 M) [11,30]
flurbiprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 3
⤷ pIC50 8.0 (IC50 1x10-8 M) [3]
(S)-ARN2508 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 28
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [28]
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 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 2x10-8 M) [7]
celecoxib 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 6.5 – 8.7 pIC50 5,20
⤷ pIC50 8.7 (IC50 2x10-9 M) [5]
pIC50 6.5 (IC50 3x10-7 M) [20]
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 7.4 pIC50 19
⤷ pIC50 7.4 (IC50 4x10-8 M) [19]
SC-58125 Small molecule or natural product Hs Inhibition 7.4 pIC50 11
⤷ pIC50 7.4 [11]
peptide 30 [PMID: 27019010] Peptide Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 33
⤷ pIC50 7.2 (IC50 6x10-8 M) [33]
tigemocoxib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 39
⤷ pIC50 7.2 (IC50 6.25x10-8 M) [39]
carprofen Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Inhibition 7.0 pIC50 14
⤷ pIC50 7.0 (IC50 1.02x10-7 M) [14]
Description: Inhibition of COX-2-induced conversion of arachadonic acid to 12-HHT.
compound 3 [Uddin et al., 2020] Small molecule or natural product Ligand has a PDB structure Mm Inhibition 6.7 pIC50 37
⤷ pIC50 6.7 (IC50 2x10-7 M) [37]
Description: Biochemical assay measuring inhibiton of purified murine COX-2.
compound 12a [PMID: 29031075] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 20
⤷ pIC50 6.6 (IC50 2.3x10-7 M) [20]
HR1405-01 Small molecule or natural product Hs Inhibition 6.5 pIC50 32
⤷ pIC50 6.5 (IC50 3x10-7 M) [32]
compound 9 [Kumar et al., 2019] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 26
⤷ pIC50 6.4 (IC50 3.67x10-7 M) [26]
Description: Inhibition of recombinant hCOX2 in vitro.
SWE101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 25
⤷ pIC50 6.4 (IC50 4.2x10-7 M) [25]
meloxicam 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 6.3 pIC50 27
⤷ pIC50 6.3 (IC50 4.9x10-7 M) [27]
rofecoxib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 – 6.5 pIC50 40
⤷ pIC50 6.1 – 6.5 [40]
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 6.2 pIC50 29
⤷ pIC50 6.2 (IC50 6x10-7 M) [29]
ketoprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.2 pIC50 8
⤷ pIC50 6.2 (IC50 6.9x10-7 M) [8]
Description: Inhibition of COX2 in human whole blood.
resveratrol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 16
⤷ pIC50 6.1 (IC50 7.5x10-7 M) [16]
compound 10 [PMID: 34279934] Small molecule or natural product Hs Inhibition 6.1 pIC50 42
⤷ pIC50 6.1 (IC50 8.4x10-7 M) [42]
Description: Inhibition of COX-2 activity in a biochemical assay
esflurbiprofen Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.0 pIC50 9
⤷ pIC50 6.0 (IC50 9.1x10-7 M) [9]
Description: Inhibition of COX-2 in human blood.
etoricoxib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.0 pIC50 31
⤷ pIC50 6.0 (IC50 1.1x10-6 M) [31]
ibuprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 38
⤷ pIC50 5.9 (IC50 1.35x10-6 M) [38]
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 5.6 pIC50 35
⤷ pIC50 5.6 (IC50 2.4x10-6 M) [35]
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 5.6 pIC50 24
⤷ pIC50 5.6 (IC50 2.5x10-6 M) [24]
indomethacin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.6 pIC50 20
⤷ pIC50 5.6 (IC50 2.63x10-6 M) [20]
ketorolac Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 4.2 – 6.9 pIC50 38
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [38]
Description: Inhibition of human COX2 measured after pre-incubation of enzyme with compound.
pIC50 4.2 (IC50 6.05x10-5 M) [38]
Description: Instantaneous inhibition of human COX2 by compound (no pre-incubation).
suprofen Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.6 pIC50 8
⤷ pIC50 5.6 (IC50 2.75x10-6 M) [8]
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 5.5 pIC50 12
⤷ pIC50 5.5 (IC50 2.9x10-6 M) [12]
FK-881 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 17
⤷ pIC50 5.5 (IC50 3.2x10-6 M) [17]
sulindac Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 43
⤷ pIC50 5.5 (IC50 3.4x10-6 M) [43]
SC-560 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.2 pIC50 34
⤷ pIC50 5.2 (IC50 6.3x10-6 M) [34]
(R)-ARN2508 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 4.6 pIC50 28
⤷ pIC50 4.6 (IC50 2.28x10-5 M) [28]
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 4.4 pIC50 22
⤷ pIC50 4.4 (IC50 3.6x10-5 M) [22]
etodolac Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Inhibition 4.3 pIC50 21
⤷ pIC50 4.3 (IC50 5.3x10-5 M) [21]
Description: Measured as LPS-induced PGE2 production in COX-1-inhibited human monocytes.
piroxicam Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 3.7 pIC50 41
⤷ pIC50 3.7 (IC50 2.18x10-4 M) [41]
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 3.5 pIC50 41
⤷ pIC50 3.5 (IC50 2.84x10-4 M) [41]
naproxcinod Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 10
⤷ [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 [13-14].
The data for etodolac in the table above is from Kato et al. (2001) [21]. In the same study etodolac's IC50 for COX-1 was reported to be >100 μM.
Piroxicam inhibits both cyclooxygenase isozymes [27], 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
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling

References

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2. 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

3. 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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