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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-12-07 02:50:26 UTC
HMDB IDHMDB0015328
Secondary Accession Numbers
  • HMDB15328
Metabolite Identification
Common NameCaptopril
DescriptionCaptopril 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
ValueSource
(2S)-1-[(2S)-2-Methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acidChEBI
AcepressChEBI
ApoprilChEBI
CapotenChEBI
CaptolaneChEBI
CaptoprilumChEBI
CaptoprylChEBI
CaptorilChEBI
CesplonChEBI
CPChEBI
D-2-Methyl-3-mercaptopropanoyl-L-prolineChEBI
D-3-mercapto-2-Methylpropanoyl-L-prolineChEBI
DilabarChEBI
GarranilChEBI
HypertilChEBI
L-CaptoprilChEBI
LopirinChEBI
TenosbonChEBI
TensobonChEBI
TensoprelChEBI
(2S)-1-[(2S)-2-Methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylateGenerator
(2S)-1-[(2S)-2-Methyl-3-sulphanylpropanoyl]pyrrolidine-2-carboxylateGenerator
(2S)-1-[(2S)-2-Methyl-3-sulphanylpropanoyl]pyrrolidine-2-carboxylic acidGenerator
(S)-1-(3-mercapto-2-Methyl-1-oxopropyl)-L-prolineMeSH
Chemical FormulaC9H15NO3S
Average Molecular Weight217.285
Monoisotopic Molecular Weight217.077264041
IUPAC Name(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Traditional Namecaptopril
CAS Registry Number62571-86-2
SMILES
C[C@H](CS)C(=O)N1CCC[C@H]1C(O)=O
InChI Identifier
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
InChI KeyFAKRSMQSSFJEIM-RQJHMYQMSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentProline and derivatives
Alternative Parents
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
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Alkylthiol
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organosulfur compound
  • Carbonyl group
  • Organic oxide
  • Organic nitrogen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Cell and elements:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

    Cardiovascular drug:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point106 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility4.52 g/LNot Available
LogP0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.52 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity54.63 m³·mol⁻¹ChemAxon
Polarizability21.72 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-9400000000-51d6dae57d8b305064acView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00fr-9410000000-65f35f9df00d94abb290View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-0940000000-26ddf220b67fb8dcdff0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-001i-0910000000-8797427ebbfead8313f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0940000000-26ddf220b67fb8dcdff0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-01b9-8910000000-d831e8d48402a4c5fe73View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01b9-9720000000-8218e12ef8f7e988c312View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0890000000-6471cadb8251b2cde228View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uk9-3920000000-93e7eef38f7bf8d57f56View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9400000000-f8b12a12ec76d0508922View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00lr-1930000000-21d83329a778cc965f80View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00yr-2910000000-30e872740f7cb996700dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-015c-9500000000-9c8558c81f9491de8c08View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Captopril PathwayPw000224Pw000224 greyscalePw000224 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01197 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01197 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01197
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID40130
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCaptopril
METLIN IDNot Available
PubChem Compound44093
PDB IDX8Z
ChEBI ID3380
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
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 ]

Enzymes

General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
General function:
Involved in metallopeptidase activity
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 vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety
Gene Name:
ACE
Uniprot ID:
P12821
Molecular weight:
149713.7
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 ]
General function:
Involved in metalloendopeptidase activity
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 type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide
Gene Name:
MMP9
Uniprot ID:
P14780
Molecular weight:
78457.5
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 ]
General function:
Involved in metalloendopeptidase activity
Specific function:
PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels
Gene Name:
MMP2
Uniprot ID:
P08253
Molecular weight:
73881.7
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 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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 ]
General function:
Involved in 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
Molecular weight:
78805.3
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 ]
General function:
Involved in ion 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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
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 ]