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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:27 UTC
HMDB IDHMDB14411
Secondary Accession NumbersNone
Metabolite Identification
Common NameDicumarol
DescriptionDicumarol is only found in individuals that have used or taken this drug. It is an oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases. [PubChem]Dicumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Structure
Thumb
Synonyms
ValueSource
3,3'-Methylen-bis(4-hydroxy-cumarin)ChEBI
3,3'-Methylene-bis(4-hydroxycoumarine)ChEBI
3,3'-Methylenebis(4-hydroxy-1,2-benzopyrone)ChEBI
3,3'-Methylenebis(4-hydroxy-2H-1-benzopyran-2-one)ChEBI
3,3'-Methylenebis(4-hydroxycoumarin)ChEBI
Bis(4-hydroxycoumarin-3-yl)methaneChEBI
Bis-3,3'-(4-hydroxycoumarinyl)methaneChEBI
Bis-hydroxycoumarinChEBI
Di-(4-hydroxy-3-coumarinyl)methaneChEBI
DicoumarolumChEBI
BishydroxycoumarinHMDB
DicoumarinHMDB
DicoumarolHMDB
Chemical FormulaC19H12O6
Average Molecular Weight336.295
Monoisotopic Molecular Weight336.063388116
IUPAC Name4-hydroxy-3-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2H-chromen-2-one
Traditional Namedicoumarol
CAS Registry Number66-76-2
SMILES
OC1=C(CC2=C(O)C3=C(OC2=O)C=CC=C3)C(=O)OC2=C1C=CC=C2
InChI Identifier
InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2
InChI KeyInChIKey=DOBMPNYZJYQDGZ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassHydroxycoumarins
Direct Parent4-hydroxycoumarins
Alternative Parents
Substituents
  • 4-hydroxycoumarin
  • 1-benzopyran
  • Benzopyran
  • Pyranone
  • Benzenoid
  • Pyran
  • Heteroaromatic compound
  • Vinylogous acid
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Anticoagulants
  • Enzyme Inhibitors
  • Uncoupling Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point290 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility6.62e-02 g/LNot Available
LogP3.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.066 mg/mLALOGPS
logP1.54ALOGPS
logP-1.6ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)-12ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area93.06 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity89.19 m3·mol-1ChemAxon
Polarizability32.32 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Dicoumarol Action PathwaySMP00656Not Available
Dicumarol PathwaySMP00270Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00266
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00266
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00266
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012523
KNApSAcK IDC00002467
Chemspider ID10183330
KEGG Compound IDC00796
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDicumarol
NuGOwiki LinkHMDB14411
Metagene LinkHMDB14411
METLIN IDNot Available
PubChem Compound54676038
PDB IDNot Available
ChEBI ID4513
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Thanos CG, Liu Z, Reineke J, Edwards E, Mathiowitz E: Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride. Pharm Res. 2003 Jul;20(7):1093-100. [12880296 ]
  2. Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, Weydert CJ, Domann FE, Oberley LW: Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. Cancer Res. 2003 Sep 1;63(17):5513-20. [14500388 ]
  3. Mironov AA, Colanzi A, Polishchuk RS, Beznoussenko GV, Mironov AA Jr, Fusella A, Di Tullio G, Silletta MG, Corda D, De Matteis MA, Luini A: Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport. Eur J Cell Biol. 2004 Jul;83(6):263-79. [15511084 ]
  4. Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz LO: Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. Arch Biochem Biophys. 2005 Feb 15;434(2):241-7. [15639223 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in zinc ion binding
Specific function:
Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species. Enhances the stability of mRNA coding for BCL2. NADPH binding interferes with mRNA binding.
Gene Name:
CRYZ
Uniprot ID:
Q08257
Molecular weight:
35206.36
References
  1. Evans PJ: Decreased intracellular proteolysis correlates with the maintenance of a specific isoenzyme of cytochrome P-450. Cell Biol Int. 1999;23(2):117-24. [10561120 ]
  2. Audi SH, Bongard RD, Dawson CA, Siegel D, Roerig DL, Merker MP: Duroquinone reduction during passage through the pulmonary circulation. Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1116-31. Epub 2003 Jul 25. [12882764 ]
  3. Asher G, Dym O, Tsvetkov P, Adler J, Shaul Y: The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol. Biochemistry. 2006 May 23;45(20):6372-8. [16700548 ]
  4. Maser E, Gebel T, Netter KJ: Carbonyl reduction of metyrapone in human liver. Biochem Pharmacol. 1991 Dec 11;42 Suppl:S93-8. [1722672 ]
  5. Hao H, Wang G, Cui N, Li J, Xie L, Ding Z: Identification of a novel intestinal first pass metabolic pathway: NQO1 mediated quinone reduction and subsequent glucuronidation. Curr Drug Metab. 2007 Feb;8(2):137-49. [17305492 ]
General function:
Involved in electron carrier activity
Specific function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO1
Uniprot ID:
P15559
Molecular weight:
30867.405
References
  1. Chen S, Wu K, Zhang D, Sherman M, Knox R, Yang CS: Molecular characterization of binding of substrates and inhibitors to DT-diaphorase: combined approach involving site-directed mutagenesis, inhibitor-binding analysis, and computer modeling. Mol Pharmacol. 1999 Aug;56(2):272-8. [10419545 ]
  2. Jaiswal AK: Characterization and partial purification of microsomal NAD(P)H:quinone oxidoreductases. Arch Biochem Biophys. 2000 Mar 1;375(1):62-8. [10683249 ]
  3. Joseph P, Jaiswal AK: A unique cytosolic activity related but distinct from NQO1 catalyses metabolic activation of mitomycin C. Br J Cancer. 2000 Apr;82(7):1305-11. [10755406 ]
  4. Floreani M, Napoli E, Palatini P: Protective action of cardiac DT-diaphorase against menadione toxicity in guinea pig isolated atria. Biochem Pharmacol. 2000 Aug 15;60(4):601-5. [10874136 ]
  5. Arriagada C, Dagnino-Subiabre A, Caviedes P, Armero JM, Caviedes R, Segura-Aguilar J: Studies of aminochrome toxicity in a mouse derived neuronal cell line: is this toxicity mediated via glutamate transmission? Amino Acids. 2000;18(4):363-73. [10949919 ]
  6. Preusch PC, Smalley DM: Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition. Free Radic Res Commun. 1990;8(4-6):401-15. [2113031 ]
General function:
Involved in vitamin-K-epoxide reductase (warfarin-sensi
Specific function:
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K.
Gene Name:
VKORC1
Uniprot ID:
Q9BQB6
Molecular weight:
18234.3
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Wallin R, Patrick SD, Ballard JO: Vitamin K antagonism of coumarin intoxication in the rat. Thromb Haemost. 1986 Apr 30;55(2):235-9. [2424118 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]