You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameFloxuridine
Accession NumberDB00322  (APRD00692)
TypeSmall Molecule
GroupsApproved
Description

An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection. Floxuridine is available as a sterile, nonpyrogenic, lyophilized powder for reconstitution. When administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. [PubChem]

Structure
Thumb
Synonyms
1-(2-Deoxy-beta-D-ribofuranosyl)-5-fluorouracil
1-beta-D-2'-Deoxyribofuranosyl-5-flurouracil
1beta-D-2'-Deoxyribofuranosyl-5-flurouracil
2'-Deoxy-5-fluorouridine
5-Fluoro-2-desoxyuridine
5-Fluorodeoxyuridine
5-Fluorouracil 2'-deoxyriboside
5-Fluorouracil deoxyriboside
5FDU
beta-5-Fluoro-2'-deoxyuridine
Deoxyfluorouridine
FdU
Floxiridina
Floxuridin
Floxuridine
Floxuridinum
Fluorodeoxyuridine
Fluoruridine Deoxyribose
FUDR
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Floxuridineinjection, powder, lyophilized, for solution500 mg/5mLintra-arterialAPP Pharmaceuticals, LLC2001-03-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
FUDRMayne
Brand mixturesNot Available
SaltsNot Available
Categories
UNII039LU44I5M
CAS number50-91-9
WeightAverage: 246.1924
Monoisotopic: 246.065199677
Chemical FormulaC9H11FN2O5
InChI KeyInChIKey=ODKNJVUHOIMIIZ-RRKCRQDMSA-N
InChI
InChI=1S/C9H11FN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1
IUPAC Name
5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
OC[[email protected]]1O[[email protected]](C[C@@H]1O)N1C=C(F)C(=O)NC1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassPyrimidine 2'-deoxyribonucleosides
Direct ParentPyrimidine 2'-deoxyribonucleosides
Alternative Parents
Substituents
  • Pyrimidine 2'-deoxyribonucleoside
  • Pyrimidone
  • Halopyrimidine
  • Pyrimidine
  • Hydropyrimidine
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Oxolane
  • Urea
  • Secondary alcohol
  • Lactam
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion).
PharmacodynamicsFloxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Floxuridine is an anti-metabolite. Anti-metabolites masquerade as pyramidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Flurouracil (the end-product of catabolism of floxuridine) blocks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the thymdine nucleotide into the DNA strand.
Mechanism of actionFloxuridine is rapidly catabolized to 5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of RNA formation through the drug's incorporation into RNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibits uracil riboside phophorylase, which prevents the utilization of preformed uracil in RNA synthesis. As well, the monophosphate of floxuridine, 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) inhibits the enzyme thymidylate synthetase. This leads to the inhibition of methylation of deoxyuridylic acid to thymidylic acid, thus interfering with DNA synthesis.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

SubstrateEnzymesProduct
Floxuridine
5-fluorouracilDetails
Floxuridine
Not Available
5,6-Dihydro-5-fluorouracilDetails
Floxuridine
Not Available
alpha-Fluoro-beta-alanineDetails
Floxuridine
Not Available
Fluoro-beta-ureidopropionateDetails
Route of eliminationThe drug is excreted intact and as urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine in the urine; it is also expired as respiratory carbon dioxide.
Half lifeNot Available
ClearanceNot Available
ToxicityOral, rat LD50: 215 mg/kg. Signs of overdose include nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, and bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9589
Blood Brain Barrier+0.768
Caco-2 permeable-0.8988
P-glycoprotein substrateNon-substrate0.7043
P-glycoprotein inhibitor INon-inhibitor0.854
P-glycoprotein inhibitor IINon-inhibitor0.888
Renal organic cation transporterNon-inhibitor0.8956
CYP450 2C9 substrateNon-substrate0.805
CYP450 2D6 substrateNon-substrate0.8668
CYP450 3A4 substrateNon-substrate0.5459
CYP450 1A2 substrateNon-inhibitor0.9125
CYP450 2C9 inhibitorNon-inhibitor0.9159
CYP450 2D6 inhibitorNon-inhibitor0.9235
CYP450 2C19 inhibitorNon-inhibitor0.9162
CYP450 3A4 inhibitorNon-inhibitor0.8926
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8378
Ames testNon AMES toxic0.6041
CarcinogenicityNon-carcinogens0.7542
BiodegradationNot ready biodegradable0.9528
Rat acute toxicity2.5247 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9508
hERG inhibition (predictor II)Non-inhibitor0.7771
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintra-arterial500 mg/5mL
Prices
Unit descriptionCostUnit
Floxuridine 500 mg vial144.0USD vial
Fudr 500 mg vial121.06USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point150.5 °CPhysProp
water solubility1.19E+004 mg/LNot Available
logP-1.16HANSCH,C ET AL. (1995)
pKa7.44SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility40.8 mg/mLALOGPS
logP-1.1ALOGPS
logP-1.3ChemAxon
logS-0.78ALOGPS
pKa (Strongest Acidic)7.68ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area99.1 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity51.26 m3·mol-1ChemAxon
Polarizability20.78 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.43 KB)
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
References
Synthesis Reference

U.S. Patent 3,041,335.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (40.5 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Floxuridine.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Floxuridine.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Floxuridine.
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Floxuridine.
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Floxuridine.
CimetidineThe serum concentration of the active metabolites of Floxuridine can be increased when Floxuridine is used in combination with Cimetidine.
ClozapineThe risk or severity of adverse effects can be increased when Floxuridine is combined with Clozapine.
DapsoneThe metabolism of Dapsone can be decreased when combined with Floxuridine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Floxuridine.
DiclofenacThe serum concentration of Diclofenac can be increased when it is combined with Floxuridine.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Floxuridine.
ErythromycinThe metabolism of Erythromycin can be decreased when combined with Floxuridine.
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Floxuridine.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Floxuridine.
GimeracilThe serum concentration of the active metabolites of Floxuridine can be increased when Floxuridine is used in combination with Gimeracil.
GliclazideThe metabolism of Gliclazide can be decreased when combined with Floxuridine.
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Floxuridine.
GlipizideThe metabolism of Glipizide can be decreased when combined with Floxuridine.
GlyburideThe metabolism of Glyburide can be decreased when combined with Floxuridine.
KetamineThe metabolism of Ketamine can be decreased when combined with Floxuridine.
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Floxuridine.
LeflunomideThe risk or severity of adverse effects can be increased when Floxuridine is combined with Leflunomide.
LosartanThe metabolism of Losartan can be decreased when combined with Floxuridine.
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Floxuridine.
MestranolThe metabolism of Mestranol can be decreased when combined with Floxuridine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Floxuridine.
NatalizumabThe risk or severity of adverse effects can be increased when Floxuridine is combined with Natalizumab.
NateglinideThe metabolism of Nateglinide can be decreased when combined with Floxuridine.
NorethisteroneThe metabolism of Norethindrone can be decreased when combined with Floxuridine.
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Floxuridine.
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Floxuridine.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Floxuridine.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Floxuridine.
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Floxuridine.
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Floxuridine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Floxuridine.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Floxuridine.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Floxuridine.
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Floxuridine.
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Floxuridine.
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Floxuridine.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Floxuridine.
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Floxuridine.
TofacitinibFloxuridine may increase the immunosuppressive activities of Tofacitinib.
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Floxuridine.
TorasemideThe metabolism of Torasemide can be decreased when combined with Floxuridine.
TrastuzumabTrastuzumab may increase the neutropenic activities of Floxuridine.
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Floxuridine.
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Floxuridine.
WarfarinThe metabolism of Warfarin can be decreased when combined with Floxuridine.
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Floxuridine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
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. Ferguson PJ, Collins O, Dean NM, DeMoor J, Li CS, Vincent MD, Koropatnick J: Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86. [PubMed:10482907 ]
  2. Kubota T: [Theoretical basis for low-dose CDDP/5-FU therapy]. Gan To Kagaku Ryoho. 1999 Oct;26(11):1536-41. [PubMed:10553409 ]
  3. Kuwa K, Sakamoto S, Sassa S, Yoshimura S, Maemura M, Nakayama T: Effects of long-term administration of UFT plus leucovorin on colorectal tumors induced with 1,2-dimethylhydrazine in rats. Anticancer Res. 1999 Nov-Dec;19(6B):5139-42. [PubMed:10697523 ]
  4. Kuwa K, Sakamoto S, Mitamura T, Kudo H, Suzuki S, Fukushima M: Effects of a low dose leucovorin with 5-fluorouracil derivative on colorectal tumors induced with 1,2-dimethylhydrazine in rats. Anticancer Res. 1999 Nov-Dec;19(6B):5143-8. [PubMed:10697524 ]
  5. Murakami Y, Kazuno H, Emura T, Tsujimoto H, Suzuki N, Fukushima M: Different mechanisms of acquired resistance to fluorinated pyrimidines in human colorectal cancer cells. Int J Oncol. 2000 Aug;17(2):277-83. [PubMed:10891536 ]

Enzymes

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. BIRNIE GD, KROEGER H, HEIDELBERGER C: STUDIES OF FLUORINATED PYRIMIDINES. XVIII. THE DEGRADATION OF 5-FLUORO-2'-DEOXYURIDINE AND RELATED COMPOUNDS BY NUCLEOSIDE PHOSPHORYLASE. Biochemistry. 1963 May-Jun;2:566-72. [PubMed:14069549 ]
  2. Tsume Y, Hilfinger JM, Amidon GL: Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm. 2008 Sep-Oct;5(5):717-27. doi: 10.1021/mp800008c. Epub 2008 Jul 25. [PubMed:18652477 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23