H+/K+ ATPase Inhibitors
19 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).
H+/K+ ATPase 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 H+/K+ ATPase 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 | Company | Approved | Indications |
|---|---|---|---|
| NEXIUM | AstraZeneca | 2001 | 7 |
| LANSOPRAZOLE | Novartis | 2009 | 6 |
| PRILOSEC | AstraZeneca | 1989 | 6 |
| NAPROXEN AND ESOMEPRAZOLE MAGNESIUM | PHARMOBEDIENT | 2020 | 5 |
| ACIPHEX | EISAI MEDCL RES | 1999 | 5 |
| PANTOPRAZOLE SODIUM | Viatris | 2007 | 4 |
| ESOMEPRAZOLE SODIUM | EUGIA PHARMA | 2013 | 4 |
| PANTOPRAZOLE SODIUM IN 0.9% SODIUM CHLORIDE | Baxter | 2024 | 4 |
| VOQUEZNA | PHATHOM PHARMACEUTICALS INC | 2023 | 4 |
| PROTONIX | Pfizer | 2000 | 4 |
| PROTONIX IV | Pfizer | 2001 | 4 |
| DEXLANSOPRAZOLE | TWI PHARMS | 2017 | 3 |
| DEXILANT | Takeda | 2009 | 3 |
| KONVOMEP | AZURITY | 2022 | 2 |
| TALICIA | TALICIA HOLDINGS | 2019 | 2 |
| VOQUEZNA DUAL PAK | PHATHOM | 2022 | 1 |
H+/K+ ATPase 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.
H+/K+ ATPase Clinical Trials 1,186 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on H+/K+ ATPase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 422 | 372 | 22 | 28 | 94% |
| Phase 2 | 174 | 106 | 29 | 39 | 79% |
| Phase 3 | 217 | 156 | 26 | 35 | 86% |
| Phase 4 | 373 | 244 | 53 | 75 | 82% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
H+/K+ ATPase Drug Approval Timeline (1999 - 2024)
Erosive or ulcerative gastroesophageal reflux disease (GERD)
Gastroesophageal Reflux Disease
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
- • 16 companies competing
- • Market share by company
Full Drug Portfolio
- • All 19 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 19-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 599 (198 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 H+/K+ ATPase. A trial counts if an approved drug acting on H+/K+ ATPase 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.