Protein / target
Prostaglandin G/H synthase 1
Protein at a glance
Biological role
Prostaglandin-endoperoxide synthase activity
Primary system
Cardiovascular system
Strongest disease association
hemorrhage
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
56 approved · 3 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975). Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
Subcellular location
Domains and Gene Ontology detail (16)Hide
Domains & features
Gene Ontology
- Ccytoplasm
- Cendoplasmic reticulum lumen
- Cendoplasmic reticulum membrane
- Cextracellular exosome
- Cneuron projection
- Cphotoreceptor outer segment
- Fheme binding
- Fmetal ion binding
- Foxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
- Fperoxidase activity
- Fprostaglandin-endoperoxide synthase activity
- Pcyclooxygenase pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis path…
Metabolic enzyme activity
- ·oxidoreductase activity, acting on single donors with incorporation of molecular oxygen,…
Haemostasis
- ·Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis path…
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Cyclooxygenase inhibitor
Appears in clinical studies involving Headache, arthritic joint disease, Muscle spasm, Pain
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,290 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 64 total
spondylitis · osteoarthritis · gout
Headache · arthritic joint disease · Muscle spasm
Pain · osteoarthritis · inflammation
osteoarthritis · rheumatoid arthritis · Pain
osteoarthritis · rheumatoid arthritis
ankylosing spondylitis · Arthralgia · rheumatic disorder
Fever · Pain
osteoarthritis · Pain · rheumatoid arthritis
Dysmenorrhea · osteoarthritis · rheumatoid arthritis
ankylosing spondylitis
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “Cyclooxygenase 1” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Supplemental approval
Supplemental approval: BUTALBITAL, ASPIRIN, CAFFEINE AND CODEINE PHOSPHATE (ANDA074951)
- Supplemental approval
Supplemental approval: OXYCODONE AND ASPIRIN (ANDA040910)
- Supplemental approval
Supplemental approval: BUTALBITAL, ASPIRIN, CAFEINE, AND CODEINE PHOSPHATE (ANDA075231)
- Label change
Label change: BUTALBITAL, ASPIRIN, CAFFEINE AND CODEINE PHOSPHATE (ANDA074951)
- Label change
Label change: BUTALBITAL, ASPIRIN, CAFEINE, AND CODEINE PHOSPHATE (ANDA075231)
- Label change
Label change: BUTALBITAL, ASPIRIN, CAFEINE, AND CODEINE PHOSPHATE (ANDA075231)
- Label change
Label change: OXYCODONE AND ASPIRIN (ANDA040910)
- Label change
Label change: BUTALBITAL, ASPIRIN, CAFFEINE AND CODEINE PHOSPHATE (ANDA074951)
- Label change
Label change: OXYCODONE AND ASPIRIN (ANDA040910)
- Supplemental approval
Supplemental approval: BUTALBITAL, ASPIRIN, CAFFEINE AND CODEINE PHOSPHATE (ANDA074951)
- Supplemental approval
Supplemental approval: OXYCODONE AND ASPIRIN (ANDA040910)
- Supplemental approval
Supplemental approval: BUTALBITAL, ASPIRIN, CAFEINE, AND CODEINE PHOSPHATE (ANDA075231)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.