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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:29:31 UTC
HMDB IDHMDB14684
Secondary Accession NumbersNone
Metabolite Identification
Common NameFluorouracil
DescriptionFluorouracil is only found in individuals that have used or taken this drug. It is a pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [PubChem]The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.
Structure
Thumb
Synonyms
ValueSource
5-FluoracilChEBI
5-Fluoropyrimidine-2,4-dioneChEBI
5-FUChEBI
FluorouraciloChEBI
FluorouracilumChEBI
5-FluorouracilHMDB
Chemical FormulaC4H3FN2O2
Average Molecular Weight130.0772
Monoisotopic Molecular Weight130.017855555
IUPAC Name5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione
Traditional Namefluorouracil
CAS Registry Number51-21-8
SMILES
FC1=CNC(=O)NC1=O
InChI Identifier
InChI=1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
InChI KeyInChIKey=GHASVSINZRGABV-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentHalopyrimidines
Alternative Parents
Substituents
  • Pyrimidone
  • Halopyrimidine
  • Hydropyrimidine
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Urea
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
  • Drug metabolite
Biofunction
  • Waste products
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point280 - 282 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.86e+00 g/LNot Available
LogP-0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.86 mg/mLALOGPS
logP-0.58ALOGPS
logP-0.66ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)7.76ChemAxon
pKa (Strongest Basic)-8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity26.17 m3·mol-1ChemAxon
Polarizability9.46 Å3ChemAxon
Number of Rings1ChemAxon
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, Positivesplash10-001i-1900000000-3fa9b91447db7dc7ba77View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01q9-9800000000-32bf878787078ce9d817View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-3ef559051a5b99c94b29View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-4900000000-82764fbca3290816328dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000f-9100000000-2da5eb3c925c027b5022View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-1cf432837297c55833a5View in MoNA
MSMass Spectrum (Electron Ionization)splash10-001i-9400000000-b8247c8f5c45b12efaa6View in MoNA
1D NMR1H NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Capecitabine Metabolism PathwaySMP00607Not Available
Capecitabine PathwaySMP00469Not Available
Fluorouracil Metabolism PathwaySMP00608Not Available
Fluorouracil PathwaySMP00470Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00544
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00544
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-8 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-4 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00544
DrugBank Metabolite IDDBMET00418
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3268
KEGG Compound IDC07649
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFluorouracil
NuGOwiki LinkHMDB14684
Metagene LinkHMDB14684
METLIN IDNot Available
PubChem Compound3385
PDB IDURF
ChEBI ID46345
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [12724731 ]
  2. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [15032669 ]

Enzymes

General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular weight:
74595.895
References
  1. Scartozzi M, Maccaroni E, Giampieri R, Pistelli M, Bittoni A, Del Prete M, Berardi R, Cascinu S: 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65. [21332317 ]
General function:
Involved in electron carrier activity
Specific function:
Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Gene Name:
DPYD
Uniprot ID:
Q12882
Molecular weight:
111400.32
Reactions
Fluorouracil + NADPH + Hydrogen Ion → 5,6-Dihydro-5-fluorouracil + NADPdetails
References
  1. Ho DH, Townsend L, Luna MA, Bodey GP: Distribution and inhibition of dihydrouracil dehydrogenase activities in human tissues using 5-fluorouracil as a substrate. Anticancer Res. 1986 Jul-Aug;6(4):781-4. [3752956 ]
  2. Keizer HJ, De Bruijn EA, Tjaden UR, De Clercq E: Inhibition of fluorouracil catabolism in cancer patients by the antiviral agent (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Cancer Res Clin Oncol. 1994;120(9):545-9. [8045919 ]
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 catalytic activity
Specific function:
Not Available
Gene Name:
UMPS
Uniprot ID:
P11172
Molecular weight:
52221.075
Reactions
Fluorouracil + Phosphoribosyl pyrophosphate → 5-Fluorouridine monophosphate + Pyrophosphatedetails
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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 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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
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 monooxygenase activity
Specific function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular weight:
56517.005
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 transferase activity, transferring glycosyl groups
Specific function:
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Gene Name:
TYMP
Uniprot ID:
P19971
Molecular weight:
49954.965
Reactions
5'-Deoxy-5-fluorouridine + Phosphoric acid → Fluorouracil + 5-Deoxyribose-1-phosphatedetails
Fluorouracil + Deoxyribose 1-phosphate → Floxuridine + Phosphoric aciddetails
References
  1. Scartozzi M, Maccaroni E, Giampieri R, Pistelli M, Bittoni A, Del Prete M, Berardi R, Cascinu S: 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65. [21332317 ]
General function:
Involved in thymidylate synthase activity
Specific function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular weight:
35715.65
References
  1. Formentini A, Sander S, Denzer S, Straeter J, Henne-Bruns D, Kornmann M: Thymidylate synthase expression in resectable and unresectable pancreatic cancer: role as predictive or prognostic marker? Int J Colorectal Dis. 2007 Jan;22(1):49-55. Epub 2006 Mar 15. [16538493 ]
  2. Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [16563096 ]
  3. Fernandez-Contreras ME, Sanchez-Prudencio S, Sanchez-Hernandez JJ, Garcia de Paredes ML, Gisbert JP, Roda-Navarro P, Gamallo C: Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil. Int J Oncol. 2006 May;28(5):1303-10. [16596248 ]
  4. Garcia V, Garcia JM, Pena C, Silva J, Dominguez G, Hurtado A, Alonso I, Rodriguez R, Provencio M, Bonilla F: Thymidylate synthase messenger RNA expression in plasma from patients with colon cancer: prognostic potential. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2095-100. [16609021 ]
  5. Ploylearmsaeng SA, Fuhr U, Jetter A: How may anticancer chemotherapy with fluorouracil be individualised? Clin Pharmacokinet. 2006;45(6):567-92. [16719540 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Rustum YM: Thymidylate synthase: a critical target in cancer therapy? Front Biosci. 2004 Sep 1;9:2467-73. [15353299 ]
  8. Scartozzi M, Maccaroni E, Giampieri R, Pistelli M, Bittoni A, Del Prete M, Berardi R, Cascinu S: 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65. [21332317 ]
General function:
Involved in transferase activity, transferring pentosyl groups
Specific function:
Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Gene Name:
UPP1
Uniprot ID:
Q16831
Molecular weight:
33934.005
Reactions
Fluorouracil + Ribose 1-phosphate → 5-Fluorouridine + Phosphoric aciddetails
References
  1. Yan R, Wan L, Pizzorno G, Cao D: Uridine phosphorylase in breast cancer: a new prognostic factor? Front Biosci. 2006 Sep 1;11:2759-66. [16720348 ]
General function:
Involved in transferase activity, transferring pentosyl groups
Specific function:
Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Shows substrate specificity and accept uridine, deoxyuridine, and thymidine as well as the two pyrimidine nucleoside analogs 5-fluorouridine and 5-fluoro-2(')-deoxyuridine as substrates.
Gene Name:
UPP2
Uniprot ID:
O95045
Molecular weight:
41601.795
Reactions
Fluorouracil + Ribose 1-phosphate → 5-Fluorouridine + Phosphoric aciddetails
References
  1. Yan R, Wan L, Pizzorno G, Cao D: Uridine phosphorylase in breast cancer: a new prognostic factor? Front Biosci. 2006 Sep 1;11:2759-66. [16720348 ]