H+, K+-ATPase Inhibitors
2 drugsAbout H+, K+-ATPase
The H+/K+ ATPase, or proton pump, is an enzyme responsible for gastric acid secretion. It is a heterodimer found in parietal cells of the stomach lining, where it exchanges potassium ions for protons to acidify the gastric lumen.
H+/K+ ATPase is a validated drug target, with moderate genetic evidence (max score 0.33) linking ATP4A variants to cholelithiasis and gallstones. Loss-of-function variants appear protective against liver disease, suggesting inhibition may be beneficial.
Nineteen FDA-approved small molecule drugs target H+/K+ ATPase, including Prilosec, Pantoprazole, and Esomeprazole. These drugs are primarily used for acid-related conditions, with applications in 'Other' therapeutic areas (17 drugs), immunology (1 drug), and infectious disease (1 drug).
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 81% attractiveness score.
- White space opportunity in Infection, Bacterial with only 3 trials.
Human Genetic Evidence Moderate
Genetic evidence provides moderate support for H+/K+ ATPase as a drug target, with a max score of 0.33.
Further investigation of ATP4A variants in liver disease could reveal novel therapeutic opportunities.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in endocrine system disease, gastrointestinal disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link ATP4A to 6 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 0.99eQTL/pQTL signals for ATP4A 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 Drugs
Fifteen companies have approved drugs targeting H+/K+ ATPase, with Dr. Reddy's, CHARTWELL RX, and ZYDUS PHARMS among the top players.
The presence of multiple generic manufacturers suggests a highly competitive landscape with potential pricing pressures.
Drug Modality Landscape
Modalities
Routes of Administration
H+, K+-ATPase is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide differentiation in a crowded market.
Clinical Trials 337 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 50 | 42 | 2 | 5 | 95% |
| Phase 2 | 44 | 26 | 3 | 15 | 90% |
| Phase 3 | 80 | 56 | 9 | 15 | 86% |
| Phase 4 | 163 | 106 | 16 | 41 | 87% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2022 - 2023)
The first drug targeting H+/K+ ATPase was approved in 1989, and the most recent in 2024, spanning 36 years.
Continued approvals indicate sustained interest in this target, but also suggest a mature market with limited whitespace.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • 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 243 clinical trials targeting H+, K+-ATPase.
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