Identification

Name
Floxuridine
Accession Number
DB00322
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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 246.1924
Monoisotopic: 246.065199677
Chemical Formula
C9H11FN2O5
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-fluoro-2'-deoxyuridine
  • 5-Fluorodeoxyuridine
  • 5-Fluorouracil 2'-deoxyriboside
  • 5-Fluorouracil deoxyriboside
  • 5FDU
  • beta-5-Fluoro-2'-deoxyuridine
  • Deoxyfluorouridine
  • FdU
  • Floxiridina
  • Floxuridin
  • Floxuridine
  • Floxuridinum
  • Fluorodeoxyuridine
  • Fluoruridine deoxyribose
External IDs
  • NSC-27640

Pharmacology

Indication

For 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).

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Floxuridine is an anti-metabolite or a pyrimidine analog that works by disrupting the process S-phase of cell division, selectively targeting rapidly dividing cells. Due to the structural similarities, antimetabolites act as pyrimidine-like molecules and prevent normal pyrimidines from being incorporated into DNA. After successful biotransformation, floxuridine is converted into an active component, flurouracil, which blocks the enzyme which converts cytosine nucleosides into the deoxy derivative. Flurouracil also physically prevents the incorporation of thymidine nucleotides into the DNA strand by taking their place, further preventing DNA synthesis.

Mechanism of action

Floxuridine rapidly undergoes catabolism to form 5-fluorouracil, which is the active component of the drug. 5-Fluorouracil primarily works by interfering with DNA synthesis; however, it may also inhibit the formation of fraudulent RNA via physical incorporation into the RNA. It is also an inhibitor of riboside phophorylase, preventing the utilization of pre-formed uracil in RNA synthesis. Floxuridine can also form 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP), which is the monophosphate of floxuridine that inhibits thymidylate synthetase that plays a role in the methylation of deoxyuridylic acid to thymidylic acid during DNA synthesis. FUDR-MP thus interferes with DNA synthesis.

TargetActionsOrganism
AThymidylate synthaseNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

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Route of elimination

Floxuridine can be excreted as unchanged drug, urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine via the kidneys. Floxuridine may also be excreted as respiratory carbon dioxide.

Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Oral, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirFloxuridine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Floxuridine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Floxuridine.
AcarboseAcarbose may decrease the excretion rate of Floxuridine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Floxuridine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Floxuridine which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Floxuridine.
AcetaminophenAcetaminophen may decrease the excretion rate of Floxuridine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Floxuridine which could result in a lower serum level and potentially a reduction in efficacy.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Floxuridine.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Purchasing individual compounds or compound libraries for your research?
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International/Other Brands
FUDR (Mayne)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FdurInjection, powder, lyophilized, for solution500 mg/5mLIntra-arterialHospira Worldwide, Inc.1970-12-182009-04-05US flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FloxuridineInjection, powder, lyophilized, for solution100 mg/1mLIntra-arterialBedford Pharmaceuticals2000-10-162012-08-31US flag
FloxuridineInjection, powder, lyophilized, for solution500 mg/5mLIntra-arterialFresenius Kabi USA, LLC2001-03-15Not applicableUS flag
FloxuridineInjection, powder, lyophilized, for solution100 mg/1mLIntra-arterialHikma Pharmaceuticals USA Inc.2018-02-15Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01BC09 — Floxuridine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Halopyrimidines / Hydroxypyrimidines / Aryl fluorides / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds
show 6 more
Substituents
Alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Halopyrimidine / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Hydroxypyrimidine
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, nucleoside analogue, pyrimidine 2'-deoxyribonucleoside (CHEBI:60761)

Chemical Identifiers

UNII
039LU44I5M
CAS number
50-91-9
InChI Key
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

References

Synthesis Reference

U.S. Patent 3,041,335.

General References
Not Available
Human Metabolome Database
HMDB0014467
KEGG Drug
D04197
KEGG Compound
C11736
PubChem Compound
5790
PubChem Substance
46508645
ChemSpider
5586
BindingDB
50340678
RxNav
4488
ChEBI
60761
ChEMBL
CHEMBL917
ZINC
ZINC000003813010
Therapeutic Targets Database
DAP001245
PharmGKB
PA449652
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Floxuridine
MSDS
Download (40.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentColorectal Cancers / Metastatic Cancers2
3Not Yet RecruitingTreatmentHepatic Metastases / Metastatic Colorectal Cancer (MCRC)1
3RecruitingTreatmentColorectal Cancers / HAI / Hepatic Metastases1
3RecruitingTreatmentColorectal Cancers / Metastasis1
3RecruitingTreatmentMetastatic Colorectal Cancer (MCRC)1
3TerminatedTreatmentColorectal Cancers / Metastatic Cancers1
2Active Not RecruitingTreatmentCholangiocarcinomas / Colorectal Cancers1
2Active Not RecruitingTreatmentCholangiocellular Carcinoma / Cholangiolar Carcinoma / Intrahepatic Cholangiocarcinoma / Peripheral Cholangiocarcinoma1
2Active Not RecruitingTreatmentColorectal Cancers / Metastatic Cancers1
2Active Not RecruitingTreatmentLiver Cancer1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Ethex Corp.
  • Hospira Inc.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntra-arterial500 mg/5mL
InjectionIntra-arterial0.5 gr
Injection, powder, lyophilized, for solutionIntra-arterial100 mg/1mL
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)150.5 °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-1.2ALOGPS
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (9.43 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-00lr-9600000000-155a97133c7827d2a1ce
GC-MS Spectrum - CI-BGC-MSsplash10-001i-3900000000-44f00976f508bab47f36
GC-MS Spectrum - CI-BGC-MSsplash10-00kb-2910000000-2efae68e874a5fdba01c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
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
Uniprot Name
Thymidylate synthase
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
Humans
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 v...
Gene Name
TYMP
Uniprot ID
P19971
Uniprot Name
Thymidine phosphorylase
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]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Gunes A, Coskun U, Boruban C, Gunel N, Babaoglu MO, Sencan O, Bozkurt A, Rane A, Hassan M, Zengil H, Yasar U: Inhibitory effect of 5-fluorouracil on cytochrome P450 2C9 activity in cancer patients. Basic Clin Pharmacol Toxicol. 2006 Feb;98(2):197-200. doi: 10.1111/j.1742-7843.2006.pto_304.x. [PubMed:16445595]
  2. Brown MC: An adverse interaction between warfarin and 5-fluorouracil: A case report and review of the literature. Chemotherapy. 1999 Sep-Oct;45(5):392-5. doi: 10.1159/000007230. [PubMed:10473927]
  3. Gilbar PJ, Brodribb TR: Phenytoin and fluorouracil interaction. Ann Pharmacother. 2001 Nov;35(11):1367-70. doi: 10.1345/aph.1A051. [PubMed:11724084]
  4. Karadag O, Babaoglu MO, Altundag K, Elkiran T, Yasar U, Bozkurt A: 5-Fluorouracil-induced coronary spasm: may inhibition of hyperpolarization factors produced by CYP2C enzymes be the cause? Oncology. 2004;66(6):510-1. doi: 10.1159/000079506. [PubMed:15452381]
  5. Up to Date: Floxuridine [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. CYTOMEL (liothyronine) FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2020 02:59

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