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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Endometrial Cancer with only 2 trials.
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 |
|---|---|---|---|
| ENALAPRIL MALEATE | KRKA DD NOVO MESTO | 2000 | 3 |
| LISINOPRIL AND HYDROCHLOROTHIAZIDE | COREPHARMA | 2002 | 3 |
| PERINDOPRIL ERBUMINE | Apotex | 2009 | 3 |
| VASOTEC | BAUSCH | 1985 | 3 |
| VASERETIC | BAUSCH | 1986 | 3 |
| MAXZIDE-25 | Aurobindo Pharma | 1984 | 3 |
| MAXZIDE | Aurobindo Pharma | 1984 | 3 |
| EPANED | AZURITY | 2016 | 3 |
| QBRELIS | AZURITY | 2016 | 3 |
| MICROZIDE | Teva | 1996 | 3 |
| ZESTRIL | TWI PHARMS | 1988 | 3 |
| ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE | SENORES PHARMS | 2001 | 2 |
| AMLODIPINE BESYLATE AND BENAZEPRIL HYDROCHLORIDE | WATSON LABS INC | 2007 | 1 |
| LOTREL | Novartis | 1995 | 1 |
| LOTENSIN | VALIDUS PHARMS | 1991 | 1 |
| LOTENSIN HCT | VALIDUS PHARMS | 1992 | 1 |
| RAMIPRIL | Cipla | 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 361 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 67 | 62 | 2 | 3 | 97% |
| Phase 2 | 69 | 45 | 15 | 9 | 75% |
| Phase 3 | 84 | 62 | 14 | 8 | 82% |
| Phase 4 | 141 | 100 | 23 | 18 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
ACE Drug Approval Timeline (1973 - 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
- • 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 183 clinical trials targeting ACE.
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