Quinapril
Explore a selection of our essential drug information below, or:
Identification
- Summary
Quinapril is an ACE inhibitor prodrug used to treat hypertension, congestive heart failure, and slow rate of progression of renal disease.
- Brand Names
- Accupril, Accuretic
- Generic Name
- Quinapril
- DrugBank Accession Number
- DB00881
- Background
Quinapril is the ethyl ester prodrug of the non-sulfhydryl angiotensin converting enzyme inhibitor quinaprilat.6,7 It is used to treat hypertension and heart failure.6,7 ACE inhibitors are commonly used as a first line therapy in the treatment of hypertension, along with thiazide diuretics or beta blockers.5
Quinapril was granted FDA approval on 19 November 1991.6 A combination tablet with hydrochlorothiazide was also approved on 28 December 1999.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 438.5161
Monoisotopic: 438.21547208 - Chemical Formula
- C25H30N2O5
- Synonyms
- Quinapril
- Quinaprilum
- External IDs
- C09AA06
Pharmacology
- Indication
Quinapril is indicated for the treatment of hypertension and as an adjunct therapy in the treatment of heart failure.6 Quinapril in combination with hydrochlorothiazide is indicated for the treatment of hypertension.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in management of Congestive heart failure •••••••••••• Management of Diabetic nephropathy ••• ••••• Used in combination to manage Hypertension Combination Product in combination with: Hydrochlorothiazide (DB00999) •••••••••••• Management of Hypertension ••• ••••• ••••••••• Management of Hypertension •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Quinapril is a prodrug of an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure.1,2,6 Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80mg once daily.6
- Mechanism of action
Angiotensin II constricts coronary blood vessels and is positively inotropic, which under normal circumstances, would increase vascular resistance and oxygen consumption.4 This action can eventually lead to myocyte hypertrophy and vascular smooth muscle cell proliferation.4 Angiotensin II also stimulates production of plasminogen activator inhibitor-1 (PAI-1), increasing the risk of thrombosis.2
Quinaprilat prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin converting enzyme, and also reduces the breakdown of bradykinin.1,2 Reduced levels of angiotensin II lead to lower levels of PAI-1, reducing the risk of thrombosis, especially after a myocardial infarction.2
Target Actions Organism AAngiotensin-converting enzyme inhibitorHumans - Absorption
Quinapril if 50-80% bioavailable.1 Quinapril has a Tmax of <1 hour,6 while quinaprilat has a Tmax of 2.5h.1 The Cmax of quinaprilat is highly variable but reaches 1526ng/mL with an AUC of 2443ng*h/mL in healthy males given a 10mg dose.1 A high fat meal reduces the absorption of quinapril by 25-30%.1
- Volume of distribution
The mean volume of distribution of quinaprilat is 13.9L.1
- Protein binding
Quinapril and the active metabolite quinaprilat are 97% protein bound in plasma.6,7
- Metabolism
Quinapril is de-esterified to the active quinaprilat or dehydrated to form the inactive PD109488.1,3 PD109488 can undergo O-deethylation to form another inactive metabolite, PD113413.1,3
Hover over products below to view reaction partners
- Route of elimination
Quinaprilat is up to 96% eliminated in the urine.6 The eliminated metabolites PD109488 and PD113413 account for approximately 6% of a dose of quinapril each.1,3 A small fraction of the dose recovered in the urine is accounted for by unmetabolized quinapril.3
- Half-life
The active metabolite quinaprilat has an elimination half life of 2.3 hours.1,6
- Clearance
The clearance of quinaprilat is 68mL/min.1
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The oral LD50 in rats is 3541mg/kg and in mice is 1739mg/kg.8
Patients experiencing an overdose may present with symptoms of severe hypotension.6,7 Due to the extensive protein binding of quinapril and the active metabolite quinaprilat, hemodialysis is not expected to remove the drug from circulation.6,7 Treat patients with symptomatic and supportive measures, including normal saline infusions to restore normal blood pressure.6,7
- Pathways
Pathway Category Quinapril Metabolism Pathway Drug metabolism Quinapril Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Quinapril is combined with Abaloparatide. Acebutolol Quinapril may increase the hypotensive activities of Acebutolol. Aceclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Quinapril. Acemetacin The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Quinapril. Acetylsalicylic acid The therapeutic efficacy of Quinapril can be decreased when used in combination with Acetylsalicylic acid. - Food Interactions
- Avoid fatty foods.
- Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
- Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
- Limit salt intake. Salt may attenuate the antihypertensive effect.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Quinapril Hydrochloride 33067B3N2M 82586-55-8 IBBLRJGOOANPTQ-JKVLGAQCSA-N - Active Moieties
Name Kind UNII CAS InChI Key Quinaprilat prodrug 34SSX5LDE5 82768-85-2 FLSLEGPOVLMJMN-YSSFQJQWSA-N - Product Images
- International/Other Brands
- Accuprin (Pfizer (Italy)) / Accupro (Pfizer (Austria, Denmark, Finland, Germany, Hungary, Ireland, Sweden, Switzerland, United Kingdom, Ukraine), Godecke (Czech Republic, Germany, Poland, Russia), Parke, Davis (Germany)) / Acequin / Acuitel / Korec / Quinazil
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Accupril Tablet, film coated 5 mg/1 Oral Parke-Davis Div of Pfizer Inc 2019-11-19 2019-11-19 US Accupril Tablet, film coated 10 mg/1 Oral Parke-Davis Div of Pfizer Inc 1991-11-19 Not applicable US Accupril Tablet, film coated 40 mg/1 Oral bryant ranch prepack 1991-11-19 2006-12-01 US Accupril Tablet, film coated 20 mg/1 Oral Parke-Davis Div of Pfizer Inc 2019-11-19 2019-11-19 US Accupril Tablet, film coated 40 mg/1 Oral Physicians Total Care, Inc. 1994-12-05 2011-06-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-quinapril Tablet 40 mg Oral Apotex Corporation 2013-07-02 Not applicable Canada Apo-quinapril Tablet 5 mg Oral Apotex Corporation 2013-07-02 Not applicable Canada Apo-quinapril Tablet 20 mg Oral Apotex Corporation 2013-07-02 Not applicable Canada Apo-quinapril Tablet 10 mg Oral Apotex Corporation 2013-07-02 Not applicable Canada Auro-quinapril Tablet 10 mg Oral Auro Pharma Inc Not applicable Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Accuretic Quinapril Hydrochloride (20 mg/1) + Hydrochlorothiazide (12.5 mg/1) Tablet, film coated Oral Parke-Davis Div of Pfizer Inc 2021-12-06 Not applicable US Accuretic Quinapril Hydrochloride (20 mg/1) + Hydrochlorothiazide (12.5 mg/1) Tablet, film coated Oral Parke-Davis Div of Pfizer Inc 1999-12-28 2022-04-30 US Accuretic Quinapril Hydrochloride (20 mg) + Hydrochlorothiazide (25 mg) Tablet Oral Pfizer Italia S.R.L. 2003-06-02 2024-04-05 Canada ACCURETIC Quinapril (20 MG) + Hydrochlorothiazide (12.5 MG) Tablet, coated Oral Pfizer Italia S.R.L. 2014-07-08 Not applicable Italy Accuretic Quinapril Hydrochloride (10 mg/1) + Hydrochlorothiazide (12.5 mg/1) Tablet, film coated Oral Parke-Davis Div of Pfizer Inc 2021-11-29 Not applicable US
Categories
- ATC Codes
- C09AA06 — Quinapril
- C09AA — ACE inhibitors, plain
- C09A — ACE INHIBITORS, PLAIN
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- ACE Inhibitors and Diuretics
- Agents Acting on the Renin-Angiotensin System
- Agents causing angioedema
- Agents causing hyperkalemia
- Angiotensin-Converting Enzyme Inhibitors
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Cardiovascular Agents
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Hypotensive Agents
- Isoquinolines
- OAT3/SLC22A8 Substrates
- Protease Inhibitors
- Tetrahydroisoquinolines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- Alpha amino acid esters / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Tetrahydroisoquinolines / Fatty acid esters / Aralkylamines / Dicarboxylic acids and derivatives / Benzene and substituted derivatives / Tertiary carboxylic acid amides / Amino acids show 8 more
- Substituents
- Alpha-amino acid amide / Alpha-amino acid ester / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- dicarboxylic acid monoester, ethyl ester, isoquinolines (CHEBI:8713)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- RJ84Y44811
- CAS number
- 85441-61-8
- InChI Key
- JSDRRTOADPPCHY-HSQYWUDLSA-N
- InChI
- InChI=1S/C25H30N2O5/c1-3-32-25(31)21(14-13-18-9-5-4-6-10-18)26-17(2)23(28)27-16-20-12-8-7-11-19(20)15-22(27)24(29)30/h4-12,17,21-22,26H,3,13-16H2,1-2H3,(H,29,30)/t17-,21-,22-/m0/s1
- IUPAC Name
- (3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
- SMILES
- CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC=CC=C2C[C@H]1C(O)=O
References
- Synthesis Reference
Om P. Goel, Uldis Krolls, "Crystalline quinapril and a process for producing the same." U.S. Patent US4761479, issued August, 1982.
US4761479- General References
- Kieback AG, Felix SB, Reffelmann T: Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1337-47. doi: 10.1517/17425250903282773. [Article]
- Tsikouris JP, Suarez JA, Meyerrose GE, Ziska M, Fike D, Smith J: Questioning a class effect: does ACE inhibitor tissue penetration influence the degree of fibrinolytic balance alteration following an acute myocardial infarction? J Clin Pharmacol. 2004 Feb;44(2):150-7. [Article]
- Kaplan HR, Taylor DG, Olson SC, Andrews LK: Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology. 1989 Apr;40(4 Pt 2):335-50. doi: 10.1177/000331978904000403. [Article]
- Goa KL, Balfour JA, Zuanetti G: Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. Drugs. 1996 Oct;52(4):564-88. doi: 10.2165/00003495-199652040-00011. [Article]
- Wright JM, Musini VM, Gill R: First-line drugs for hypertension. Cochrane Database Syst Rev. 2018 Apr 18;4:CD001841. doi: 10.1002/14651858.CD001841.pub3. [Article]
- FDA Approved Drug Products: Quinapril Oral Tablet [Link]
- FDA Approved Drug Products: Quinapril and Hydrochlorothiazide Oral Tablets [Link]
- Cayman Chemicals: Quinapril MSDS [Link]
- Pfizer Canada: Quinapril Oral Tablets [Link]
- External Links
- Human Metabolome Database
- HMDB0015019
- KEGG Drug
- D03752
- KEGG Compound
- C07398
- PubChem Compound
- 54892
- PubChem Substance
- 46506309
- ChemSpider
- 49565
- BindingDB
- 50368166
- 35208
- ChEBI
- 8713
- ChEMBL
- CHEMBL1592
- ZINC
- ZINC000003801163
- Therapeutic Targets Database
- DAP000588
- PharmGKB
- PA451205
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Quinapril
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Healthy Volunteers (HV) 2 somestatus stop reason just information to hide Not Available Completed Not Available Hypertension 1 somestatus stop reason just information to hide Not Available Completed Treatment Arterial Occlusive Diseases 1 somestatus stop reason just information to hide Not Available Completed Treatment Diabetes / Hypertension 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Pfizer pharmaceuticals ltd
- Actavis totowa llc
- Apotex inc
- Genpharm inc
- Invagen pharmaceuticals inc
- Lupin ltd
- Mylan pharmaceuticals inc
- Ranbaxy laboratories ltd
- Sandoz inc
- Sun pharmaceutical industries ltd
- Teva pharmaceuticals usa inc
- Watson laboratories inc florida
- Packagers
- Actavis Group
- Apotex Inc.
- A-S Medication Solutions LLC
- Atlantic Biologicals Corporation
- Aurobindo Pharma Ltd.
- Cardinal Health
- Direct Dispensing Inc.
- Dispensing Solutions
- Doctor Reddys Laboratories Ltd.
- Eon Labs
- Goedecke GmbH
- Greenstone LLC
- Heartland Repack Services LLC
- InvaGen Pharmaceuticals Inc.
- Lupin Pharmaceuticals Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Ohm Laboratories Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmacia Inc.
- Physicians Total Care Inc.
- Prepackage Specialists
- Ranbaxy Laboratories
- Rebel Distributors Corp.
- Resource Optimization and Innovation LLC
- Southwood Pharmaceuticals
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Tablet, coated Oral 10 mg Tablet, coated Oral 40 mg Tablet Oral 5 mg Tablet Oral 10 mg Tablet Oral 20 mg Tablet Oral 40 mg Injection, solution Intravenous 5 mg Tablet, film coated Oral 10 mg Tablet, film coated Oral 20 mg Tablet, film coated Oral 5 MG Tablet, film coated Oral Tablet Oral 10 mg/1 Tablet Oral 20 mg/1 Tablet Oral 40 mg/1 Tablet Oral 5 mg/1 Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 40 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, coated Oral Tablet, film coated Oral Tablet Oral Injection, solution Intravenous 5 MG/5ML Solution Intravenous 5 mg Tablet, film coated Oral 40 MG Tablet, coated Oral 20 mg Tablet, coated Oral 5 mg - Prices
Unit description Cost Unit Accupril 10 mg tablet 2.02USD tablet Accupril 20 mg tablet 2.02USD tablet Accupril 40 mg tablet 2.02USD tablet Accupril 5 mg tablet 2.02USD tablet Quinapril 10 mg tablet 1.57USD tablet Quinapril 20 mg tablet 1.57USD tablet Quinapril 40 mg tablet 1.57USD tablet Quinapril 5 mg tablet 1.57USD tablet Quinapril HCl 10 mg tablet 1.27USD tablet Quinapril HCl 20 mg tablet 1.27USD tablet Quinapril HCl 40 mg tablet 1.27USD tablet Quinapril HCl 5 mg tablet 1.27USD tablet Quinaretic 10-12.5 mg tablet 1.27USD tablet Quinaretic 20-12.5 mg tablet 1.27USD tablet Quinaretic 20-25 mg tablet 1.27USD tablet Accupril 10 mg Tablet 0.96USD tablet Accupril 20 mg Tablet 0.96USD tablet Accupril 40 mg Tablet 0.96USD tablet Accupril 5 mg Tablet 0.96USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5684016 No 1997-11-04 2015-05-04 US CA2023089 No 2003-01-14 2010-08-10 Canada CA1331615 No 1994-08-23 2011-08-23 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 120-130 °C Chemspider logP 0.86 Pfizer Canada Monograph pKa 2.8 Pfizer Canada Monograph - Predicted Properties
Property Value Source Water Solubility 0.0085 mg/mL ALOGPS logP 1.4 ALOGPS logP 1.96 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.7 Chemaxon pKa (Strongest Basic) 5.2 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 95.94 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 119.96 m3·mol-1 Chemaxon Polarizability 47.36 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.5597 Blood Brain Barrier - 0.9409 Caco-2 permeable - 0.8208 P-glycoprotein substrate Substrate 0.8895 P-glycoprotein inhibitor I Inhibitor 0.7344 P-glycoprotein inhibitor II Inhibitor 0.5869 Renal organic cation transporter Non-inhibitor 0.8258 CYP450 2C9 substrate Non-substrate 0.8594 CYP450 2D6 substrate Non-substrate 0.8412 CYP450 3A4 substrate Substrate 0.5356 CYP450 1A2 substrate Non-inhibitor 0.8597 CYP450 2C9 inhibitor Non-inhibitor 0.6832 CYP450 2D6 inhibitor Non-inhibitor 0.8636 CYP450 2C19 inhibitor Non-inhibitor 0.6016 CYP450 3A4 inhibitor Inhibitor 0.5347 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5162 Ames test Non AMES toxic 0.9091 Carcinogenicity Non-carcinogens 0.9294 Biodegradation Not ready biodegradable 0.9596 Rat acute toxicity 2.2690 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9763 hERG inhibition (predictor II) Inhibitor 0.7176
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 225.6050325 predictedDarkChem Lite v0.1.0 [M-H]- 195.3161 predictedDeepCCS 1.0 (2019) [M+H]+ 225.4173325 predictedDarkChem Lite v0.1.0 [M+H]+ 197.71169 predictedDeepCCS 1.0 (2019) [M+Na]+ 225.8529325 predictedDarkChem Lite v0.1.0 [M+Na]+ 203.62419 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- 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)
- Specific Function
- actin binding
- Gene Name
- ACE
- Uniprot ID
- P12821
- Uniprot Name
- Angiotensin-converting enzyme
- Molecular Weight
- 149713.675 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Culy CR, Jarvis B: Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs. 2002;62(2):339-85. [Article]
- Klutchko S, Blankley CJ, Fleming RW, Hinkley JM, Werner AE, Nordin I, Holmes A, Hoefle ML, Cohen DM, Essenburg AD, et al.: Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types. J Med Chem. 1986 Oct;29(10):1953-61. [Article]
- Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
- Specific Function
- carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- Tarkiainen EK, Tornio A, Holmberg MT, Launiainen T, Neuvonen PJ, Backman JT, Niemi M: Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8. doi: 10.1111/bcp.12667. Epub 2015 Jun 11. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Shi JH, Pan DQ, Jiang M, Liu TT, Wang Q: In vitro study on binding interaction of quinapril with bovine serum albumin (BSA) using multi-spectroscopic and molecular docking methods. J Biomol Struct Dyn. 2017 Aug;35(10):2211-2223. doi: 10.1080/07391102.2016.1213663. Epub 2016 Aug 7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (By similarity) (PubMed:15521010, PubMed:18367661, PubMed:19685173, PubMed:26320580, PubMed:7896779, PubMed:8914574, PubMed:9835627). Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system (PubMed:15521010, PubMed:9835627)
- Specific Function
- dipeptide transmembrane transporter activity
- Gene Name
- SLC15A1
- Uniprot ID
- P46059
- Uniprot Name
- Solute carrier family 15 member 1
- Molecular Weight
- 78805.265 Da
References
- Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides (PubMed:16434549, PubMed:18367661, PubMed:7756356). Transports neutral and anionic dipeptides with a proton to peptide stoichiometry of 2:1 or 3:1 (By similarity). In kidney, involved in the absorption of circulating di- and tripeptides from the glomerular filtrate (PubMed:7756356). Can also transport beta-lactam antibiotics, such as the aminocephalosporin cefadroxil, and other antiviral and anticancer drugs (PubMed:16434549). Transports the dipeptide-like aminopeptidase inhibitor bestatin (By similarity). Also able to transport carnosine (PubMed:31073693). Involved in innate immunity by promoting the detection of microbial pathogens by NOD-like receptors (NLRs) (By similarity). Mediates transport of bacterial peptidoglycans across the plasma membrane or, in macrophages, the phagosome membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand (PubMed:20406817)
- Specific Function
- dipeptide transmembrane transporter activity
- Gene Name
- SLC15A2
- Uniprot ID
- Q16348
- Uniprot Name
- Solute carrier family 15 member 2
- Molecular Weight
- 81782.77 Da
References
- Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Quinaprilat is the active metabolite of quinapril; its substrate profile was demonstrated in vitro using HEK293 cells.
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 19:35