ACE Inhibitors
20 drugsAbout ACE
Angiotensin-converting enzyme (ACE) is a key component of the renin-angiotensin-aldosterone system (RAAS), regulating blood pressure and fluid balance. It catalyzes the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. ACE is a well-validated drug target, particularly in cardiovascular therapeutics.
Human genetic studies provide strong support for ACE as a therapeutic target (max score 0.89), with variants linked to renal tubular dysgenesis, intracerebral hemorrhage and diabetic nephropathy. Loss-of-function variants are associated with increased risk, suggesting activation may be beneficial.
ACE is targeted by 20 FDA-approved small molecule drugs, including Hydrochlorothiazide, Zestril and Enalapril Maleate. These drugs are primarily used for cardiovascular conditions (19 drugs), with one drug approved for another therapeutic area. Twelve companies have approved ACE-targeting drugs.
ACE Genetic Evidence Strong
Genetic evidence strongly supports ACE's role in diseases like renal tubular dysgenesis (score 0.89).
Strong genetic support suggests that clinical trials targeting ACE have a higher likelihood of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in urinary system disease, nervous system disease, cardiovascular disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link ACE to 27 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for ACE 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 ACE Drugs
Twelve companies have approved ACE-targeting drugs, with Senores Pharms and Jubilant Cadista among the top players.
The presence of multiple players indicates a competitive market, requiring a strong value proposition for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LISINOPRIL | Aurobindo Pharma | 2002 | 3 |
| PERINDOPRIL ERBUMINE | Hikma | 2009 | 3 |
| VASOTEC | BAUSCH | 1985 | 3 |
| ENALAPRIL MALEATE | UNIQUE PHARM | 2000 | 3 |
| MICROZIDE | Teva | 1996 | 3 |
| LISINOPRIL AND HYDROCHLOROTHIAZIDE | MACLEODS PHARMS | 2002 | 3 |
| VASERETIC | BAUSCH | 1986 | 3 |
| QBRELIS | AZURITY | 2016 | 3 |
| EPANED | AZURITY | 2016 | 3 |
| MAXZIDE-25 | Aurobindo Pharma | 1984 | 3 |
| MAXZIDE | Aurobindo Pharma | 1984 | 3 |
| ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE | MPP PHARMA | 2001 | 2 |
| AMLODIPINE BESYLATE AND BENAZEPRIL HYDROCHLORIDE | WATSON LABS | 2007 | 1 |
| LOTENSIN HCT | VALIDUS PHARMS | 1992 | 1 |
| LOTREL | Novartis | 1995 | 1 |
| LOTENSIN | VALIDUS PHARMS | 1991 | 1 |
| RAMIPRIL | Lupin | 2005 | - |
ACE Drug Modality Landscape
Modalities
Routes of Administration
ACE is amenable to small molecule drugs, with oral options available for convenient dosing.
Explore novel modalities like antibodies or gene therapies to differentiate from existing ACE inhibitors.
ACE Clinical Trials 362 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on ACE. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 67 | 62 | 2 | 3 | 97% |
| Phase 2 | 69 | 45 | 14 | 10 | 76% |
| Phase 3 | 85 | 61 | 15 | 9 | 80% |
| Phase 4 | 141 | 99 | 23 | 19 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
ACE Drug Approval Timeline (1984 - 2016)
The first ACE-targeting drug was approved in 1973, with the most recent approval in 2025, spanning 53 years.
The continued approval of ACE inhibitors suggests ongoing innovation and market demand in this therapeutic area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 14 companies competing
- • Market share by company
Full Drug Portfolio
- • All 20 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 20-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 199 (53 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 ACE. A trial counts if an approved drug acting on ACE 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.