ACE angiotensin I converting enzyme
ENSG00000159640 · protein coding · Open Targets profile
Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, PubMed:7523412, PubMed:7683654). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:10913258, PubMed:1320019, PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:11432860, PubMed:1851160, PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (PubMed:15615692, PubMed:2558109, PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). Catalyzes degradation of different enkephalin neuropeptides (Met- enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met- enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, PubMed:656131). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin- Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met- enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:10336644, PubMed:19773553, PubMed:7876104). {ECO:0000250|UniProtKB:P09470, ECO:0000269|PubMed:10336644, ECO:0000269|PubMed:10913258, ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:11604391, ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:15615692, ECO:0000269|PubMed:16154999, ECO:0000269|PubMed:18077343, ECO:0000269|PubMed:1851160, ECO:0000269|PubMed:19773553, ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:23056909, ECO:0000269|PubMed:2558109, ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:2982830, ECO:0000269|PubMed:2983326, ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465, ECO:0000269|PubMed:6208535, ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131, ECO:0000269|PubMed:7523412, ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104, ECO:0000269|PubMed:8257427, ECO:0000269|PubMed:8609242, ECO:0000269|PubMed:9371719}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7516899704933167 (upper bound 0.8736400008201599). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 65 registry trials, updated in the last three years, of the most advanced drugs against ACE (cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spirapril), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alberto ZanchettiIstituto Auxologico Italiano. Milan. Italy · 1 of 1 trials Phase 2+
- Alejandro BalestracciHospital General de Niños Pedro de Elizalde · 1 of 1 trials Phase 2+
- Alexandra KonradiAlmazov National Medical Research Centre - Department of Hypertension, Saint Petersburg, Russia · 1 of 1 trials Phase 2+
- Alisse HauspurgWOMEN AND INFANTS HOSPITAL-RHODE ISLAND · 1 of 1 trials Phase 2+
- Ashish R SatavMAHAN Trust · 1 of 1 trials Phase 2+
- Bret GoodpasterTranslational Research Institute, Advent Health · 1 of 1 trials Phase 2+
- Colin McArthurMedical Research Institute of New Zealand, Study Chair REMAP-CAP New Zealand · 1 of 1 trials Phase 2+
- Derek AngusUniversity of Pittsburgh Medical Center, Study Chair REMAP-CAP USA · 1 of 1 trials Phase 2+
- Diana KarpmanRegion Skane · 1 of 1 trials Phase 2+
- Dorairaj PrabhakaranCentre for Chronic Disease Control, New Delhi · 1 of 1 trials Phase 2+
- Felix José JA RamiresInstituto do Coração - INCORHCFMUSP · 1 of 1 trials Phase 2+
- Francois GUEYFFIERHospices Civils de Lyon · 1 of 1 trials Phase 2+
- Gail K AdlerBrigham and Women's Hospital · 1 of 1 trials Phase 2+
- Hui LiuSun yat-sen universtiy cancer center · 1 of 1 trials Phase 2+
- Jay DinermanHeart Center Research, LLC · 1 of 1 trials Phase 2+
Registry trials of cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spirapril updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 57 of 61 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 4 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
34 trials of drugs against ACE were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spirapril, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 34.
- terminated · 2025-05-06 · Sunnybrook Health Sciences Centre · matched by the registry's drug synonyms“Lack of recruitment.”
- withdrawn · 2025-02-17 · Nova Scotia Health Authority · Intralesional enalaprilat injection“Study never began, it did not proceed beyond an initial REB review”
- terminated · 2024-11-06 · University of Alberta · labetalol/hydralazine/enalapril“Slow enrolment after publication of the Interact III study”
- terminated · 2024-02-28 · Penn State University · Enalapril Pill“COVID shut down human subjects research and then the grant funding expired”
- terminated · 2024-02-20 · Istituto Auxologico Italiano · enalapril tablets“Because of delay in approval of the protocol by a number of Ethics Commitees the trial was terminated on March 4, 2010. No patient had received any study drug.”
- terminated · 2023-10-24 · Novartis · Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1, Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2, Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter, Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1, Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2, Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter“The study was terminated early because of significant efficacy results for the primary endpoint in favor of benazepril/amlodipine treatment.”
- terminated · 2023-10-18 · Institut de Recherches Internationales Servier · matched by the registry's drug synonyms“for strategic reasons”
- suspended · 2021-05-06 · University of Cape Town · matched by the registry's drug synonyms“COVID and Funding”
- terminated · 2020-08-19 · Odense University Hospital · matched by the registry's drug synonyms“No effect of the ACE inhibitor evaluated halfway in the study”
- suspended · 2020-06-30 · National University of Ireland, Galway, Ireland · matched by the registry's drug synonyms“Challenges with funding and very low incidence of COVID-19 at Irish study site”
- withdrawn · 2019-06-21 · Charles University, Czech Republic · matched by the registry's drug synonyms“Insufficient funds”
- terminated · 2019-03-26 · Rennes University Hospital · matched by the registry's drug synonymsNo reason given
- withdrawn · 2018-10-11 · Brigham and Women's Hospital · Enalapril“Lost funding prior to study commencing”
- terminated · 2018-08-28 · Wake Forest University Health Sciences · benazepril hydrochloride“slow accrual”
- withdrawn · 2018-01-11 · Vanderbilt University Medical Center · Enalapril 10 mg bid“Study is being redesigned and submitted as a new study.”
- terminated · 2017-09-28 · Duke University · matched by the registry's drug synonyms“Following an interim analysis the study team felt that there was enough data that showed no significant difference.”
- terminated · 2017-08-03 · Gene PreDiT · matched by the registry's drug synonyms“Unproven hypothesis”
- terminated · 2017-05-11 · KU Leuven · matched by the registry's drug synonymsNo reason given
- terminated · 2017-02-24 · Haukeland University Hospital · Enalapril“Lack of financing of the study drug. Not sufficient financial support.”
- terminated · 2016-08-15 · Novartis Pharmaceuticals · Enalapril 10 mg BID“Early termination was approved due to compelling efficacy of LCZ696 in patients with HF \& reduced EF after final pre-specified interim analysis 28-Mar-2014.”
- terminated · 2016-06-28 · Meir Medical Center · Lercanidipine/enalapril fixed combination“sponsor decision”
- terminated · 2016-04-05 · Nanfang Hospital, Southern Medical University · Benazepril, Benazepril+Losartan“Significant differences observed between groups.”
- terminated · 2016-02-24 · Institut National de la Santé Et de la Recherche Médicale, France · matched by the registry's drug synonyms“recruitement problem”
- withdrawn · 2016-01-20 · Shenzhen Ausa Pharmed Co.,Ltd · Enalapril maleate and folic acid tablets, Enalapril maleate“The sponsor and the PIs both agreed that the CSPPT-CKD should be a sub-study of the CSPPT insted of an independent randomized trial.”
- withdrawn · 2015-10-06 · The Hospital for Sick Children · matched by the registry's drug synonyms“no participants enrolled”
Paediatric incentives and obligations for ACE's drugs
For cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spirapril: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · ACE is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-003186-PIP01-22 (Indapamide;perindopril arginine, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 10 Jun 2022; EMEA-003173-PIP01-21 (amlodipine;atorvastatin;Indapamide;perindopril arginine, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 20 May 2022; EMEA-001706-PIP01-14-M03 (Enalapril (maleate), Treatment of heart failure): PM: decision on the application for modification of an agreed PIP, 17 Mar 2021; compliance positive 25 Jun 2021; EMEA-003015-PIP01-21 (Indapamide;perindopril arginine;amlodipine;bisoprolol (fumarate), Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 8 Sept 2021; +13 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spiraprilRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Aqumeldi: authorised since 15 Nov 2023Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Aqumeldi, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spiraprilRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 49 interventional studies of cilazapril, enalapril, perindopril arginine, enalaprilat, delapril, benazepril, moexipril, imidapril, quinapril, perindopril erbumine, fosinopril, spirapril include patients under 18; 3 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 24 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.