COX-1 Inhibitors
28 drugsAbout COX-1
Cyclooxygenase-1 (COX-1), encoded by the PTGS1 gene, is a constitutively expressed enzyme that produces prostaglandins involved in various physiological processes. As a 'housekeeping' enzyme, it maintains normal cellular function in most tissues by synthesizing signaling molecules.
Human genetics provide moderate support for COX-1 as a drug target, with a maximum genetic score of 0.54 linking loss-of-function variants to protection against squamous cell carcinoma. Inhibition of COX-1 is likely beneficial based on genetic evidence.
COX-1 is targeted by 28 FDA-approved small molecule drugs, including EC-NAPROSYN, NAPROSYN, and XIFYRM. These drugs are primarily used for pain (10 drugs) and immunology (9 drugs) indications.
COX-1 Genetic Evidence Moderate
Genetic evidence offers moderate support for COX-1 as a target, with a top score of 0.54.
Further investigation of squamous cell carcinoma genetics may reveal novel therapeutic opportunities.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 2 traits
- • Strong signal in cancer or benign tumor, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
2 totalGWAS and other genetic studies link PTGS1 to 2 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 2 strong
max H4: 1.00eQTL/pQTL signals for PTGS1 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top COX-1 Drugs
The COX-1 drug market includes 23 companies, with NOVITIUM PHARMA and Lupin among the leaders.
The fragmented market suggests opportunities for consolidation or targeted drug development.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| NAPROXEN AND ESOMEPRAZOLE MAGNESIUM | AJANTA PHARMA LTD | 2020 | 5 |
| DICLOFENAC SODIUM AND MISOPROSTOL | YUNG SHIN PHARM | 2012 | 4 |
| ARTHROTEC | Pfizer | 1997 | 4 |
| FLECTOR | IBSA | 2007 | 4 |
| MELOXICAM | Lupin | 2004 | 3 |
| DAYPRO | Pfizer | 1992 | 3 |
| LICART | IBSA INST BIO | 2018 | 3 |
| COXANTO | SOLUBIOMIX | 2023 | 3 |
| BROMFENAC SODIUM | AMRING PHARMS | 2011 | 2 |
| PROLENSA | BAUSCH AND LOMB INC | 2013 | 2 |
| CALDOLOR | CUMBERLAND PHARMS | 2009 | 2 |
| CAMBIA | COSETTE | 2009 | 2 |
| MEFENAMIC ACID | MICRO LABS LTD | 2010 | 2 |
| SUMATRIPTAN AND NAPROXEN SODIUM | RISING | 2018 | 2 |
| PONSTEL | AVION PHARMS | 1967 | 2 |
| BROMSITE | Sun Pharma | 2016 | 2 |
| FELDENE | Pfizer | 1982 | 2 |
| OMIDRIA | RAYNER SURGICAL | 2014 | 2 |
| QAMZOVA | NANJING DELOVA | 2025 | 1 |
| SPRIX | COSETTE | 2010 | 1 |
| COMBOGESIC | AFT PHARMS US | 2023 | 1 |
| SYMBRAVO | AXSOME | 2025 | 1 |
| COMBOGESIC IV | Hikma | 2023 | 1 |
| ZIPSOR | COSETTE | 2009 | 1 |
| XIFYRM | AZURITY | 2025 | 1 |
COX-1 Drug Modality Landscape
Modalities
Routes of Administration
COX-1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide differentiation.
COX-1 Clinical Trials 1,516 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 296 | 245 | 26 | 24 | 90% |
| Phase 2 | 329 | 231 | 56 | 39 | 80% |
| Phase 3 | 321 | 243 | 40 | 34 | 86% |
| Phase 4 | 570 | 386 | 100 | 79 | 79% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved COX-1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting COX-1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
COX-1 Drug Approval Timeline (1967 - 2025)
Approved COX-1 drugs span from PONSTEL in 1967 to XIFYRM in 2025, a 59-year period.
The continued approvals indicate sustained interest, but recent approvals may signal market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 23 companies competing
- • Market share by company
Full Drug Portfolio
- • All 28 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 28-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 1056 clinical trials targeting COX-1.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities