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Identification
NameFluorouracil
Accession NumberDB00544  (APRD00516, EXPT03204)
TypeSmall Molecule
GroupsApproved
Description

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]

Structure
Thumb
Synonyms
5-Fluoracil
5-Fluoropyrimidine-2,4-dione
5-Fluorouracil
5-Fluracil
5-FU
Fluoro Uracil
Fluorouracil
Fluorouracilo
Fluorouracilum
Fluouracil
FU
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Adrucilsolution50 mgintravenousPfizer Canada Inc1995-12-312004-04-08Canada
Adrucil Inj 50mg/mlliquid500 mgintravenousAdria Laboratories Of Canada Ltd.1978-12-311996-09-10Canada
Caraccream5 mg/gtopicalDermik Laboratories2000-10-272015-11-30Us
Caraccream5 mg/gtopicalValeant Pharmaceuticals North America LLC2013-06-28Not applicableUs
Efudexcream2 g/40gtopicalValeant Pharmaceuticals North America LLC1970-07-29Not applicableUs
Efudex Crm 5%cream5 %topicalValeant Canada Lp Valeant Canada S.E.C.1975-12-31Not applicableCanada
Fluoroplexcream10 mg/gtopicalAqua Pharmaceuticals, LLC1993-12-03Not applicableUs
Fluoroplex Cream 1%cream1 %topicalAllergan Herbert Skin Care Division Of Allergan Inc.1992-12-312011-08-04Canada
Fluorouracilsolution20 mg/mLtopicalSolco Healthcare US LLC2010-06-01Not applicableUs
Fluorouracilsolution50 mg/mLtopicalSolco Healthcare US LLC2010-06-01Not applicableUs
Fluorouracilcream5 mg/gtopicalMylan Pharmaceuticals Inc.2013-07-23Not applicableUs
Fluorouracilcream5 mg/gtopicalSpear Dermatology Products Inc2014-10-28Not applicableUs
Fluorouracil Inj 50mg/mlliquid50 mgintravenousDavid Bull Laboratories (Pty) Ltd.1993-12-311996-09-10Canada
Fluorouracil Injectionsolution50 mgintravenousSandoz Canada Incorporated1989-12-31Not applicableCanada
Fluorouracil Injectionsolution5 gintravenousAccord Healthcare Inc2014-10-01Not applicableCanada
Fluorouracil Injection USPsolution50 mgintravenousHospira Healthcare Corporation1998-11-25Not applicableCanada
Tolakcream.04 g/gtopicalHill Dermaceuticals, Inc.2015-08-28Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Adrucilinjection5 g/100mLintravenousTeva Parenteral Medicines, Inc.2003-10-01Not applicableUs
Adrucilinjection2.5 g/50mLintravenousTeva Parenteral Medicines, Inc.2003-10-01Not applicableUs
Adrucilinjection, solution50 mg/mLintravenousTeva Parenteral Medicines, Inc.2003-10-01Not applicableUs
Fluorouracilcream50 mg/gtopicalPhysicians Total Care, Inc.2011-09-06Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-07-18Not applicableUs
Fluorouracilcream50 mg/gtopicalSpear Dermatology Products2008-04-11Not applicableUs
Fluorouracilcream50 mg/gtopicalTaro Pharmaceutical Industries Ltd.2010-03-05Not applicableUs
Fluorouracilcream50 mg/gtopicalTaro Pharmaceuticals U.S.A., Inc.2010-03-05Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousBlue Point Laboratories2014-12-15Not applicableUs
Fluorouracilsolution50 mg/mLtopicalTaro Pharmaceuticals U.S.A., Inc.2003-11-05Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousSandoz Inc2011-05-02Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-07-18Not applicableUs
Fluorouracilsolution20 mg/mLtopicalTaro Pharmaceuticals U.S.A., Inc.2003-11-05Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousSandoz Inc2008-09-10Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-07-18Not applicableUs
Fluorouracilcream50 mg/gtopicalRebel Distributors Corp2008-04-11Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousFresenius Kabi USA, LLC2000-07-12Not applicableUs
Fluorouracilcream5 mg/gtopicalSpear Dermatology Products2015-04-23Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-07-18Not applicableUs
Fluorouracilinjection, solution50 mg/mLintravenousAccord Healthcare, Inc.2014-02-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CarzonalTobishi
EfudixMeda
EfurixValeant
FtoruracilVerofarm
Brand mixtures
NameLabellerIngredients
ActikerallCipher Pharmaceuticals Inc
SaltsNot Available
Categories
UNIIU3P01618RT
CAS number51-21-8
WeightAverage: 130.0772
Monoisotopic: 130.017855555
Chemical FormulaC4H3FN2O2
InChI KeyInChIKey=GHASVSINZRGABV-UHFFFAOYSA-N
InChI
InChI=1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
IUPAC Name
5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
FC1=CNC(=O)NC1=O
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
Pharmacology
IndicationFor the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid.
PharmacodynamicsFluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.
Mechanism of actionThe 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.
Related Articles
Absorption28-100%
Volume of distributionNot Available
Protein binding8-12%
Metabolism

Hepatic. The catabolic metabolism of fluorouracil results in degradation products ( e.g., CO2, urea and α-fluoro-ß-alanine) which are inactive.

Route of eliminationSeven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour. The remaining percentage of the administered dose is metabolized, primarily in the liver.
Half life10-20 minutes
ClearanceNot Available
ToxicityLD50=230mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Fluorouracil Metabolism PathwayDrug metabolismSMP00608
Capecitabine Metabolism PathwayDrug metabolismSMP00607
Capecitabine Action PathwayDrug actionSMP00469
Fluorouracil Action PathwayDrug actionSMP00470
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Thymidylate synthase
Gene symbol: TYMS
UniProt: P04818
rs34743033 TSER*2Not AvailableNeutropenia, diarrhea16818689
Uridine 5'-monophosphate synthase
Gene symbol: UMPS
UniProt: P11172
rs1801019 Not AvailableC AlleleNeutropenia, diarrhea16818689
Dihydropyrimidine dehydrogenase [NADP(+)]
Gene symbol: DPYD
UniProt: Q12882
rs1801265 Not AvailableC alleleNausea, vomiting, reduced white cell count17848752
Dihydropyrimidine dehydrogenase [NADP(+)]
Gene symbol: DPYD
UniProt: Q12882
rs1801159 Not AvailableG alleleNausea, vomiting, reduced white cell count17848752
Glutathione S-transferase P
Gene symbol: GSTP1
UniProt: P09211
rs1695 Not AvailableA alleleHematological toxicity, gastrointestinal toxicity18540691
Dihydropyrimidine dehydrogenase [NADP(+)]
Gene symbol: DPYD
UniProt: Q12882
rs3918290 Not AvailableA alleleLeukopenia, diarrhea, mucositis18299612
Dihydropyrimidine dehydrogenase [NADP(+)]
Gene symbol: DPYD
UniProt: Q12882
rs67376798 Not AvailableT > APatients are at a higher risk of toxicity23603345
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9605
Blood Brain Barrier+0.9791
Caco-2 permeable-0.7583
P-glycoprotein substrateNon-substrate0.7752
P-glycoprotein inhibitor INon-inhibitor0.8991
P-glycoprotein inhibitor IINon-inhibitor1.0
Renal organic cation transporterNon-inhibitor0.9053
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9658
CYP450 2D6 inhibitorNon-inhibitor0.9361
CYP450 2C19 inhibitorNon-inhibitor0.9688
CYP450 3A4 inhibitorNon-inhibitor0.9661
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9839
Ames testNon AMES toxic0.8941
CarcinogenicityNon-carcinogens0.9288
BiodegradationNot ready biodegradable0.922
Rat acute toxicity2.2529 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9685
hERG inhibition (predictor II)Non-inhibitor0.9325
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Valeant pharmaceuticals international
  • Allergan herbert skin care div allergan inc
  • Spear pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Pharmacia and upjohn co
  • Teva parenteral medicines inc
  • Abic ltd
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Ebewe pharma ges mbh nfg kg
  • Marchar laboratories inc ltd
  • Smith and nephew solopak div smith and nephew
  • Watson laboratories inc
  • Elorac inc
  • Taro pharmaceuticals usa inc
Packagers
Dosage forms
FormRouteStrength
Solutiontopical
Injectionintravenous2.5 g/50mL
Injectionintravenous5 g/100mL
Liquidintravenous500 mg
Creamtopical5 mg/g
Creamtopical2 g/40g
Creamtopical5 %
Creamtopical10 mg/g
Creamtopical1 %
Creamtopical50 mg/g
Injection, solutionintravenous50 mg/mL
Solutiontopical20 mg/mL
Solutiontopical50 mg/mL
Liquidintravenous50 mg
Solutionintravenous5 g
Solutionintravenous50 mg
Creamtopical.04 g/g
Prices
Unit descriptionCostUnit
Efudex 5% Cream 40 gm Tube478.39USD tube
Fluoroplex 1% Cream 30 gm Tube268.61USD tube
Fluorouracil 5% Cream 40 gm Tube249.98USD tube
Carac 0.5% Cream 30 gm Tube209.77USD tube
Efudex 5% Solution 10ml Bottle136.51USD bottle
Fluorouracil 5% Solution 10ml Bottle115.78USD bottle
Fluorouracil 2% Solution 10ml Bottle78.63USD bottle
Efudex 5% cream10.28USD g
Fluorouracil 5% cream9.62USD g
Fluorouracil powder8.45USD g
Fluoroplex 1% cream7.85USD g
Carac cream6.43USD g
Efudex 50 mg/g Cream0.9USD g
Fluorouracil 50 mg/ml Solution0.52USD ml
Adrucil 50 mg/ml vial0.4USD ml
Fluorouracil 5000 mg/100 ml0.28USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6670335 No2001-06-022021-06-02Us
US7169401 No2003-07-182023-07-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point282-283Heidelberger, C. and Duschinsky, R.; US. Patent 2,802,005; August 6, 1957. Heidelberger, C. and Duschinsky, R.; U.S.Patent 2,885,396; May 5, 1959.
water solubility1.11E+004 mg/L (at 22 °C)BURR,A & BUNDGAARD,H (1985)
logP-0.89HANSCH,C ET AL. (1995)
logS-1.07ADME Research, USCD
pKa8.02SANGSTER (1994)
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
Mass Spec (NIST)Download (7.93 KB)
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
References
Synthesis Reference

Leroy B. Townsend, Robert A. Earl, Steven J. Manning, “Method of synthesizing 1-(tetrahydro-2-furanyl)-5-fluorouracil.” U.S. Patent US3960864, issued October, 1969.

US3960864
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. [PubMed: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. [PubMed:15032669 ]
External Links
ATC CodesL01BC02L01BC52
AHFS Codes
  • 10:00.00
  • 84:92.00
PDB Entries
FDA labelDownload (378 KB)
MSDSDownload (74 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Fluorouracil.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Fluorouracil.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Fluorouracil.
CimetidineThe serum concentration of Fluorouracil can be increased when it is combined with Cimetidine.
ClozapineThe risk or severity of adverse effects can be increased when Fluorouracil is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Fluorouracil.
DiclofenacThe serum concentration of Diclofenac can be increased when it is combined with Fluorouracil.
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Fluorouracil.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Fluorouracil.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Fluorouracil.
GemcitabineThe serum concentration of Fluorouracil can be increased when it is combined with Gemcitabine.
GimeracilThe serum concentration of Fluorouracil can be increased when it is combined with Gimeracil.
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Fluorouracil.
LeflunomideThe risk or severity of adverse effects can be increased when Fluorouracil is combined with Leflunomide.
LeucovorinThe risk or severity of adverse effects can be increased when Leucovorin is combined with Fluorouracil.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Fluorouracil.
MetronidazoleThe serum concentration of Fluorouracil can be increased when it is combined with Metronidazole.
NatalizumabThe risk or severity of adverse effects can be increased when Fluorouracil is combined with Natalizumab.
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Fluorouracil.
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Fluorouracil.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Fluorouracil.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Fluorouracil.
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Fluorouracil.
RoflumilastRoflumilast may increase the immunosuppressive activities of Fluorouracil.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Fluorouracil.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Fluorouracil.
SorafenibThe serum concentration of Fluorouracil can be decreased when it is combined with Sorafenib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fluorouracil.
TofacitinibFluorouracil may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Fluorouracil.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Fluorouracil.
Food Interactions
  • Vitamin B1 needs increased with long term use.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
other/unknown
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:16609021 ]
  5. Ploylearmsaeng SA, Fuhr U, Jetter A: How may anticancer chemotherapy with fluorouracil be individualised? Clin Pharmacokinet. 2006;45(6):567-92. [PubMed:16719540 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Rustum YM: Thymidylate synthase: a critical target in cancer therapy? Front Biosci. 2004 Sep 1;9:2467-73. [PubMed:15353299 ]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5. [PubMed:18979208 ]
  2. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. [PubMed:9264308 ]
  3. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [PubMed:12724731 ]
  4. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [PubMed:15032669 ]
3. RNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
References
  1. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5. [PubMed:18979208 ]
  2. Ghoshal K, Jacob ST: An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol. 1997 Jun 1;53(11):1569-75. [PubMed:9264308 ]
  3. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [PubMed:12724731 ]
  4. Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [PubMed:15032669 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transferase activity, transferring pentosyl 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 Da
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. doi: 10.2217/pgs.10.167. [PubMed:21332317 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase 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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization 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 Da
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. [PubMed: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. [PubMed:8045919 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Uridine phosphorylase activity
Specific Function:
Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate (PubMed:7488099). 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 Da
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. [PubMed:16720348 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Uridine phosphorylase activity
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-fluorourid...
Gene Name:
UPP2
Uniprot ID:
O95045
Molecular Weight:
35526.93 Da
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. [PubMed:16720348 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase 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:
56501.005 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase 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...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein complex binding
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 Da
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. doi: 10.2217/pgs.10.167. [PubMed:21332317 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
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. doi: 10.2217/pgs.10.167. [PubMed:21332317 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Orotidine-5'-phosphate decarboxylase activity
Specific Function:
Not Available
Gene Name:
UMPS
Uniprot ID:
P11172
Molecular Weight:
52221.075 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Metal ion binding
Specific Function:
Not Available
Gene Name:
PPAT
Uniprot ID:
Q06203
Molecular Weight:
57398.52 Da
References
  1. Link [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Sulkowska A, Bojko B, Rownicka J, Sulkowski W: Competition of drugs to serum albumin in combination therapy. Biopolymers. 2004 Jun 15;74(3):256-62. [PubMed:15150801 ]
  2. Bertucci C, Ascoli G, Uccello-Barretta G, Di Bari L, Salvadori P: The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD, and 1H and 19F NMR investigation. J Pharm Biomed Anal. 1995 Aug;13(9):1087-93. [PubMed:8573632 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Kobayashi Y, Ohshiro N, Sakai R, Ohbayashi M, Kohyama N, Yamamoto T: Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8. [PubMed:15901346 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Nucleoside transmembrane transporter activity
Specific Function:
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs).
Gene Name:
SLC29A1
Uniprot ID:
Q99808
Molecular Weight:
50218.805 Da
References
  1. Tsujie M, Nakamori S, Nakahira S, Takahashi Y, Hayashi N, Okami J, Nagano H, Dono K, Umeshita K, Sakon M, Monden M: Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer. Anticancer Res. 2007 Jul-Aug;27(4B):2241-9. [PubMed:17695509 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Yuan J, Lv H, Peng B, Wang C, Yu Y, He Z: Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10. doi: 10.1007/s00280-008-0838-z. Epub 2008 Sep 27. [PubMed:18820913 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity).
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular Weight:
169341.14 Da
References
  1. Hagmann W, Jesnowski R, Faissner R, Guo C, Lohr JM: ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44. doi: 10.1159/000178884. Epub 2008 Dec 13. [PubMed:19077464 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
May be an organic anion pump relevant to cellular detoxification.
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular Weight:
149525.33 Da
References
  1. Hagmann W, Jesnowski R, Faissner R, Guo C, Lohr JM: ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44. doi: 10.1159/000178884. Epub 2008 Dec 13. [PubMed:19077464 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name:
ABCC5
Uniprot ID:
O15440
Molecular Weight:
160658.8 Da
References
  1. Hagmann W, Jesnowski R, Faissner R, Guo C, Lohr JM: ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44. doi: 10.1159/000178884. Epub 2008 Dec 13. [PubMed:19077464 ]
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Drug created on June 13, 2005 07:24 / Updated on July 27, 2016 01:58