Identification

Name
Captopril
Accession Number
DB01197  (APRD00164)
Type
Small Molecule
Groups
Approved
Description

Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.

Structure
Thumb
Synonyms
  • (2S)-1-[(2S)-2-Methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
  • Acepress
  • Apopril
  • Captolane
  • Captoprilum
  • Captopryl
  • Captoril
  • Cesplon
  • CP
  • D-2-Methyl-3-mercaptopropanoyl-L-proline
  • D-3-Mercapto-2-methylpropanoyl-L-proline
  • Dilabar
  • Garranil
  • Hypertil
  • L-Captopril
  • Lopirin
  • Tenosbon
  • Tensobon
  • Tensoprel
External IDs
C09AA01 / SA-333 / SQ 14,225 / SQ-14225
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bci Captopril TabletsTablet50 mgOralBaker Cummins IncNot applicableNot applicableCanada
Bci Captopril TabletsTablet12.5 mgOralBaker Cummins IncNot applicableNot applicableCanada
Bci Captopril TabletsTablet100 mgOralBaker Cummins IncNot applicableNot applicableCanada
Bci Captopril TabletsTablet25 mgOralBaker Cummins IncNot applicableNot applicableCanada
CapotenTablet100 mg/1OralPar Pharmaceutical1981-04-062011-08-31Us
CapotenTablet12.5 mg/1OralPar Pharmaceutical1981-04-062011-08-31Us
CapotenTablet50 mg/1OralPar Pharmaceutical1981-04-062011-08-31Us
CapotenTablet50 mg/1OralPhysicians Total Care, Inc.1981-04-062011-05-31Us
CapotenTablet25 mg/1OralPar Pharmaceutical1981-04-062011-08-31Us
CapotenTablet12.5 mg/1OralPhysicians Total Care, Inc.1981-04-062011-07-18Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-capto Tab 100mgTablet100 mgOralApotex Corporation1990-12-31Not applicableCanada
Apo-capto Tab 12.5mgTablet12.5 mgOralApotex Corporation1990-12-31Not applicableCanada
Apo-capto Tab 25mgTablet25 mgOralApotex Corporation1990-12-31Not applicableCanada
Apo-capto Tab 50mgTablet50 mgOralApotex Corporation1990-12-31Not applicableCanada
Apo-capto Tab 6.25mgTablet6.25 mgOralApotex Corporation1992-12-31Not applicableCanada
CaptoprilTablet25 mg/1OralSt. Marys Medical Park Pharmacy2014-04-212016-07-31Us
CaptoprilTablet50 mg/1OralApotex Corporation2005-12-07Not applicableUs
CaptoprilTablet15 mg/1OralRed Pharm Drug, Inc.1996-02-13Not applicableUs67296 067720180907 15195 1werzrz
CaptoprilTablet50 mg/1OralWockhardt1997-03-28Not applicableUs
CaptoprilTablet12.5 mg/1OralMed Pharma Co., Ltd.2011-06-012012-11-08Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CapozideCaptopril (50 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralPar Pharmaceutical2006-06-162008-06-16Us
CapozideCaptopril (25 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPar Pharmaceutical2006-06-162008-06-16Us
CapozideCaptopril (50 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPar Pharmaceutical2006-06-162008-06-16Us
CapozideCaptopril (25 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralPar Pharmaceutical2006-06-162008-06-16Us
Captopril and HydrochlorothiazideCaptopril (50 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralMylan Pharmaceuticals1997-12-29Not applicableUs
Captopril and HydrochlorothiazideCaptopril (25 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralEndo Pharmaceuticals1997-12-292004-01-31Us
Captopril and HydrochlorothiazideCaptopril (50 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralTeva1997-12-302012-02-28Us
Captopril and HydrochlorothiazideCaptopril (25 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPhysicians Total Care, Inc.2007-07-12Not applicableUs
Captopril and HydrochlorothiazideCaptopril (25 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralTeva1997-12-302011-12-31Us
Captopril and HydrochlorothiazideCaptopril (50 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralEndo Pharmaceuticals1997-12-292003-05-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CapozideCaptopril (25 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralPhysicians Total Care, Inc.1996-05-142011-05-31Us
CapozideCaptopril (50 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPhysicians Total Care, Inc.1997-01-032002-06-30Us
International/Other Brands
Acepress (Bernofarm (Indonesia), BMS (Italy)) / Acepril (BMS (United Kingdom)) / Alopresin / Apopril / Capoten (Bristol-Myers Squibb, Par) / Captolane (Sanofi-Aventis (France)) / Captoril (Novopharm (Canada)) / Cesplon (Esteve (Spain)) / Dilabar (Qualigen (Spain)) / Garranil (Aristegui (Spain)) / Hipertil (Normal (Portugal)) / Hypertil (Normal (Portugal)) / Lopirin (BMS (Germany,Switzerland)) / Lopril (Orion (Finland), BMS (France)) / Tenosbon / Tensoprel (Rubio (Spain))
Categories
UNII
9G64RSX1XD
CAS number
62571-86-2
Weight
Average: 217.285
Monoisotopic: 217.077264041
Chemical Formula
C9H15NO3S
InChI Key
FAKRSMQSSFJEIM-RQJHMYQMSA-N
InChI
InChI=1S/C9H15NO3S/c1-6(5-14)8(11)10-4-2-3-7(10)9(12)13/h6-7,14H,2-5H2,1H3,(H,12,13)/t6-,7+/m1/s1
IUPAC Name
(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
SMILES
C[C@H](CS)C(=O)N1CCC[C@H]1C(O)=O

Pharmacology

Indication

For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, β-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.

Associated Conditions
Pharmacodynamics

Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.

Mechanism of action

There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Captopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Captopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI.

TargetActionsOrganism
AAngiotensin-converting enzyme
inhibitor
Human
U72 kDa type IV collagenase
inhibitor
Human
UMatrix metalloproteinase-9
inhibitor
Human
ULeukotriene A-4 hydrolase
inhibitor
Human
UB1 bradykinin receptorNot AvailableHuman
Absorption

60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)

Volume of distribution
Not Available
Protein binding

25-30% bound to plasma proteins, primarily albumin

Metabolism

Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion.

Route of elimination
Not Available
Half life

2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Captopril Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Captopril.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Captopril.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Captopril.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Captopril.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acetylsalicylic acid is combined with Captopril.
AcyclovirThe excretion of Captopril can be decreased when combined with Acyclovir.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Captopril.
Agrostis gigantea pollenThe risk or severity of adverse effects can be increased when Captopril is combined with Agrostis gigantea pollen.
Agrostis stolonifera pollenThe risk or severity of adverse effects can be increased when Captopril is combined with Agrostis stolonifera pollen.
AlclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Captopril.
Food Interactions
  • Captopril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
  • Food decreases absorption by 25 - 40%. Clinical significance is debatable.
  • Herbs that may attenuate the antihypertensive effect of captopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of captopril.

References

Synthesis Reference

Charles M. Zepp, "Methods for preparing captopril and its analogues." U.S. Patent US5166361, issued July, 1981.

US5166361
General References
  1. Atkinson AB, Robertson JI: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836-9. [PubMed:90928]
  2. Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. [PubMed:6253826]
  3. Smith CG, Vane JR: The discovery of captopril. FASEB J. 2003 May;17(8):788-9. [PubMed:12724335]
External Links
Human Metabolome Database
HMDB0015328
KEGG Drug
D00251
PubChem Compound
44093
PubChem Substance
46506879
ChemSpider
40130
BindingDB
21642
ChEBI
3380
ChEMBL
CHEMBL1560
Therapeutic Targets Database
DAP000589
PharmGKB
PA448780
HET
X8Z
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Captopril
ATC Codes
C09AA01 — CaptoprilC09BA01 — Captopril and diuretics
AHFS Codes
  • 24:32.04 — Angiotensin-converting Enzyme Inhibitors
PDB Entries
1j37 / 2x8z / 3lus / 4c1d / 4c1f / 4c1h / 4c2p / 4dpr / 4exs / 4pqa
show 1 more
MSDS
Download (37.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentGlioblastomas1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1Not Yet RecruitingDiagnosticCardiomyopathy With Unknown Etiology1
1TerminatedBasic ScienceHigh Blood Pressure (Hypertension) / Multiple System Atrophy (MSA) / Progressive autonomic failure1
1WithdrawnPreventionShigellosis1
1WithdrawnTreatmentCutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides and Sezary Syndrome / Stage IIB Mycosis Fungoides and Sezary Syndrome / Stage IIIA Mycosis Fungoides and Sezary Syndrome / Stage IIIB Mycosis Fungoides and Sezary Syndrome / Stage IVA Mycosis Fungoides and Sezary Syndrome / Stage IVB Mycosis Fungoides and Sezary Syndrome1
1, 2CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2RecruitingBasic ScienceType 2 Diabetes Mellitus1
2Not Yet RecruitingDiagnosticRadiotherapy Side Effect / Taking Captopril1
2RecruitingTreatmentAcute myeloid leukaemia (in remission) / Aplastic Anaemia (AA) / Chronic Myelomonocytic Leukemia / Indolent Non-Hodgkin's Lymphomas / Leukemia Acute Myeloid Leukemia (AML) / Lymphoma, Hodgkins / Myelodysplastic Syndrome / Myeloproliferative Neoplasms / Neoplasms, Malignant / Plasma Cell Myeloma / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Ring Sideroblasts / Refractory Cytopenia With Multilineage Dysplasia / Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts1
2TerminatedSupportive CareLung Cancers / Pulmonary Complications / Radiation Fibrosis1
2TerminatedTreatmentPemphigus Vulgaris (PV)1
2Unknown StatusTreatmentHeart Diseases1
2, 3CompletedTreatmentDiabetic Nephropathies1
3CompletedSupportive CareCancers1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentPsoriasis2
3RecruitingPreventionAcute Myeloid Leukemia in Children / Bone Tumors / Cardiotoxicity1
4CompletedNot AvailableType 2 Diabetes Mellitus1
4CompletedDiagnosticHyperaldosteronism1
4CompletedHealth Services ResearchKidney Diseases1
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Induction of intra-operative hypotension1
4CompletedTreatmentPreeclampsia1
4Unknown StatusTreatmentAortic Valve Stenosis1
Not AvailableCompletedOtherHyperparathyroidism1
Not AvailableRecruitingPreventionDiabetes, Diabetes Mellitus Type 11
Not AvailableUnknown StatusNot AvailableArterial Hypertension / Diabetes Mellitus (DM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Apotheca Inc.
  • Apothecon
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Changzhou Pharmaceutical Factory
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • E.R. Squibb and Sons LLC
  • Egis Pharmaceuticals Public Ltd. Co.
  • Eon Labs
  • Heartland Repack Services LLC
  • Innovative Manufacturing and Distribution Services Inc.
  • Lake Erie Medical and Surgical Supply
  • Legacy Pharmaceuticals Packaging LLC
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Stason Pharmaceuticals Inc.
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral12.5 mg
TabletOral25 mg
TabletOral50 mg
TabletOral6.25 mg
TabletOral100 mg/1
TabletOral12.5 mg/1
TabletOral15 mg/1
TabletOral25 mg/1
TabletOral30 mg/1
TabletOral50 mg/1
TabletOral
Prices
Unit descriptionCostUnit
Captopril powder22.03USD g
Capoten 100 mg tablet4.53USD tablet
Capoten 12.5 mg tablet1.8USD tablet
Captopril 100 mg tablet1.53USD tablet
Captopril 50 mg tablet1.14USD tablet
Capoten 25 mg tablet1.13USD tablet
Capoten 50 mg tablet1.13USD tablet
Apo-Capto 100 mg Tablet1.09USD tablet
Mylan-Captopril 100 mg Tablet1.09USD tablet
Novo-Captoril 100 mg Tablet1.09USD tablet
Nu-Capto 100 mg Tablet1.09USD tablet
Captopril 25 mg tablet0.67USD tablet
Captopril 12.5 mg tablet0.62USD tablet
Apo-Capto 50 mg Tablet0.59USD tablet
Mylan-Captopril 50 mg Tablet0.59USD tablet
Novo-Captoril 50 mg Tablet0.59USD tablet
Nu-Capto 50 mg Tablet0.59USD tablet
Apo-Capto 25 mg Tablet0.31USD tablet
Mylan-Captopril 25 mg Tablet0.31USD tablet
Novo-Captoril 25 mg Tablet0.31USD tablet
Nu-Capto 25 mg Tablet0.31USD tablet
Apo-Capto 12.5 mg Tablet0.22USD tablet
Mylan-Captopril 12.5 mg Tablet0.22USD tablet
Novo-Captoril 12.5 mg Tablet0.22USD tablet
Nu-Capto 12.5 mg Tablet0.22USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5238924No1993-08-242010-08-24Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)103-104Ondetti, M.A. and Cushman, D.W.; U.S. Patent 4,046,889; September 6, 1977; assigned t o E.R. Squibb & Sons, Inc. Ondetti, M.A. and Cushman, D.W.; U.S. Patent 4,105,776; August 8,1978; assigned to E.R. Squibb & Sons, Inc. Ondetti, M.A. and Cushman, D.W.; U.S. Patent 4,154,840; May 15,1979; assigned to E.R. Squibb & Sons, Inc.
water solubilityFreely solubleNot Available
logP0.34RANADIVE,SA ET AL. (1992)
Predicted Properties
PropertyValueSource
Water Solubility4.52 mg/mLALOGPS
logP1.02ALOGPS
logP0.73ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)4.02ChemAxon
pKa (Strongest Basic)-1.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.61 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity54.63 m3·mol-1ChemAxon
Polarizability21.72 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.97
Blood Brain Barrier+0.6467
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.6276
P-glycoprotein inhibitor INon-inhibitor0.8448
P-glycoprotein inhibitor IINon-inhibitor0.7415
Renal organic cation transporterNon-inhibitor0.8073
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.6293
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9102
CYP450 2D6 inhibitorNon-inhibitor0.9537
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9049
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8975
Ames testNon AMES toxic0.8164
CarcinogenicityNon-carcinogens0.9434
BiodegradationNot ready biodegradable0.6577
Rat acute toxicity1.7403 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9604
hERG inhibition (predictor II)Non-inhibitor0.9118
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0910000000-8797427ebbfead8313f9
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0940000000-26ddf220b67fb8dcdff0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01b9-8910000000-d831e8d48402a4c5fe73
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9720000000-8218e12ef8f7e988c312

Taxonomy

Description
This compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resulting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Proline and derivatives
Alternative Parents
N-acyl-L-alpha-amino acids / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Tertiary carboxylic acid amides / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Alkylthiols / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / N-acyl-l-alpha-amino acid / Proline or derivatives / N-acylpyrrolidine / Pyrrolidine carboxylic acid / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine / Tertiary carboxylic acid amide / Carboxamide group
show 15 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
L-proline derivative, alkanethiol, pyrrolidinemonocarboxylic acid, N-acylpyrrolidine (CHEBI:3380)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
Molecular Weight
149713.675 Da
References
  1. Andujar-Sanchez M, Jara-Perez V, Camara-Artigas A: Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method. FEBS Lett. 2007 Jul 24;581(18):3449-54. Epub 2007 Jun 27. [PubMed:17618628]
  2. Dalkas GA, Marchand D, Galleyrand JC, Martinez J, Spyroulias GA, Cordopatis P, Cavelier F: Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme. J Pept Sci. 2010 Feb;16(2):91-7. doi: 10.1002/psc.1201. [PubMed:20014331]
  3. Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR: Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. [PubMed:15236580]
  4. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. [PubMed:11030016]
  5. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [PubMed:11929321]
  6. Tzakos AG, Naqvi N, Comporozos K, Pierattelli R, Theodorou V, Husain A, Gerothanassis IP: The molecular basis for the selection of captopril cis and trans conformations by angiotensin I converting enzyme. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5084-7. Epub 2006 Aug 2. [PubMed:16889963]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rup...
Gene Name
MMP2
Uniprot ID
P08253
Uniprot Name
72 kDa type IV collagenase
Molecular Weight
73881.695 Da
References
  1. Brower GL, Levick SP, Janicki JS: Inhibition of matrix metalloproteinase activity by ACE inhibitors prevents left ventricular remodeling in a rat model of heart failure. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3057-64. Epub 2007 Feb 16. [PubMed:17308006]
  2. Okada M, Kikuzuki R, Harada T, Hori Y, Yamawaki H, Hara Y: Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats. J Pharmacol Sci. 2008 Dec;108(4):487-94. Epub 2008 Dec 5. [PubMed:19057128]
  3. Prontera C, Mariani B, Rossi C, Poggi A, Rotilio D: Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma. Int J Cancer. 1999 May 31;81(5):761-6. [PubMed:10328230]
  4. Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR: Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart. 2002 Nov;88(5):525-30. [PubMed:12381651]
  5. Williams RN, Parsons SL, Morris TM, Rowlands BJ, Watson SA: Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models. Eur J Surg Oncol. 2005 Nov;31(9):1042-50. Epub 2005 Jul 1. [PubMed:15993560]
  6. Yamamoto D, Takai S, Hirahara I, Kusano E: Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy. Clin Chim Acta. 2010 May 2;411(9-10):762-4. doi: 10.1016/j.cca.2010.02.059. Epub 2010 Feb 22. [PubMed:20184869]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves...
Gene Name
MMP9
Uniprot ID
P14780
Uniprot Name
Matrix metalloproteinase-9
Molecular Weight
78457.51 Da
References
  1. Okada M, Kikuzuki R, Harada T, Hori Y, Yamawaki H, Hara Y: Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats. J Pharmacol Sci. 2008 Dec;108(4):487-94. Epub 2008 Dec 5. [PubMed:19057128]
  2. Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR: Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart. 2002 Nov;88(5):525-30. [PubMed:12381651]
  3. Williams RN, Parsons SL, Morris TM, Rowlands BJ, Watson SA: Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models. Eur J Surg Oncol. 2005 Nov;31(9):1042-50. Epub 2005 Jul 1. [PubMed:15993560]
  4. Yamamoto D, Takai S, Miyazaki M: Inhibitory profiles of captopril on matrix metalloproteinase-9 activity. Eur J Pharmacol. 2008 Jul 7;588(2-3):277-9. doi: 10.1016/j.ejphar.2008.04.031. Epub 2008 May 22. [PubMed:18501888]
Details
4. Leukotriene A-4 hydrolase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
Gene Name
LTA4H
Uniprot ID
P09960
Uniprot Name
Leukotriene A-4 hydrolase
Molecular Weight
69284.64 Da
References
  1. Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom J: Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors. FASEB J. 2002 Oct;16(12):1648-50. Epub 2002 Aug 7. [PubMed:12207002]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Peptide binding
Specific Function
This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
Gene Name
BDKRB1
Uniprot ID
P46663
Uniprot Name
B1 bradykinin receptor
Molecular Weight
40494.29 Da
References
  1. Ignjatovic T, Tan F, Brovkovych V, Skidgel RA, Erdos EG: Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. Epub 2002 Mar 5. [PubMed:11880373]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Keire DA, Mariappan SV, Peng J, Rabenstein DL: Nuclear magnetic resonance studies of the binding of captopril and penicillamine by serum albumin. Biochem Pharmacol. 1993 Sep 14;46(6):1059-69. [PubMed:8216349]
  2. Lin SY, Wei YS, Li MJ, Wang SL: Effect of ethanol or/and captopril on the secondary structure of human serum albumin before and after protein binding. Eur J Pharm Biopharm. 2004 May;57(3):457-64. [PubMed:15093593]
  3. Mariee AD, Al-Shabanah O: Protective ability and binding affinity of captopril towards serum albumin in an in vitro glycation model of diabetes mellitus. J Pharm Biomed Anal. 2006 May 3;41(2):571-5. Epub 2006 Feb 15. [PubMed:16469467]
  4. Narazaki R, Harada K, Sugii A, Otagiri M: Kinetic analysis of the covalent binding of captopril to human serum albumin. J Pharm Sci. 1997 Feb;86(2):215-9. [PubMed:9040098]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Watanabe K, Sawano T, Terada K, Endo T, Sakata M, Sato J: Studies on intestinal absorption of sulpiride (1): carrier-mediated uptake of sulpiride in the human intestinal cell line Caco-2. Biol Pharm Bull. 2002 Jul;25(7):885-90. [PubMed:12132663]
  2. Temple CS, Boyd CA: Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter. Biochim Biophys Acta. 1998 Aug 14;1373(1):277-81. [PubMed:9733984]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate profile was determined in vitro using HEK293 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [PubMed:9880528]
  2. 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. [PubMed:19953504]

Drug created on June 13, 2005 07:24 / Updated on September 24, 2018 02:40