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 |
|---|---|---|---|
| EC-NAPROSYN | ATNAHS PHARMA US | 1994 | 9 |
| DICLOFENAC SODIUM AND MISOPROSTOL | YUNG SHIN PHARM | 2012 | 4 |
| FLECTOR | IBSA | 2007 | 4 |
| ARTHROTEC | Pfizer | 1997 | 4 |
| MELOXICAM | AIPING PHARM INC | 2004 | 3 |
| LICART | IBSA INST BIO | 2018 | 3 |
| COXANTO | SOLUBIOMIX | 2023 | 3 |
| DAYPRO | Pfizer | 1992 | 3 |
| FELDENE | Pfizer | 1982 | 2 |
| BROMFENAC SODIUM | RISING | 2011 | 2 |
| CALDOLOR | Apotex | 2009 | 2 |
| OMIDRIA | RAYNER SURGICAL | 2014 | 2 |
| PONSTEL | AVION PHARMS | 1967 | 2 |
| MEFENAMIC ACID | AJENAT PHARMS | 2010 | 2 |
| SUMATRIPTAN AND NAPROXEN SODIUM | Sun Pharma | 2018 | 2 |
| CAMBIA | COSETTE | 2009 | 2 |
| PROLENSA | BAUSCH AND LOMB INC | 2013 | 2 |
| BROMSITE | Sun Pharma | 2016 | 2 |
| SPRIX | COSETTE | 2010 | 1 |
| XIFYRM | AZURITY | 2025 | 1 |
| COMBOGESIC | AFT PHARMS US | 2023 | 1 |
| SYMBRAVO | AXSOME | 2025 | 1 |
| QAMZOVA | NANJING DELOVA | 2025 | 1 |
| ZIPSOR | COSETTE | 2009 | 1 |
| COMBOGESIC IV | Hikma | 2023 | 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 1,604 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on COX-1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 313 | 257 | 29 | 26 | 90% |
| Phase 2 | 345 | 243 | 55 | 45 | 82% |
| Phase 3 | 337 | 253 | 43 | 38 | 85% |
| Phase 4 | 609 | 407 | 105 | 97 | 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
- • 22 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
- • Sponsors: 715 (195 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on COX-1. A trial counts if an approved drug acting on COX-1 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.