NAV

Floxuridine

Identification

Summary

Floxuridine is an antimetabolite used as palliative management for liver metastases of gastrointestinal malignancy.

Generic Name
Floxuridine
DrugBank Accession Number
DB00322
Background

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
3D
Similar Structures
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
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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).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofStage 4 gastrointestinal adenocarcinoma••••••••••••••••••••• ••••••
Associated Therapies
Contraindications & Blackbox Warnings
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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.

Hover over products below to view reaction partners

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
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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).

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
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.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Floxuridine.
AceclofenacAceclofenac may decrease the excretion rate of Floxuridine which could result in a higher serum level.
Food Interactions
No interactions found.

Products

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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
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FloxuridineInjection, powder, lyophilized, for solution100 mg/1mLIntra-arterialHikma Pharmaceuticals USA Inc.2018-02-15Not applicableUS flag
FloxuridineInjection, powder, lyophilized, for solution500 mg/1Intra-arterialCerona Therapeutics, Inc.2022-06-09Not applicableUS flag
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

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)
Affected organisms
  • Humans and other mammals

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
OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(F)C(=O)NC1=O

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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedTreatmentColorectal Cancer / Metastatic Cancer2
3Not Yet RecruitingTreatmentHepatic Metastases / Stage IV Colorectal Cancer / Stage IV Colorectal Cancer AJCC v8 / Unresectable Colorectal Carcinoma1
3RecruitingTreatmentMetastatic Colorectal Cancer (CRC)1
3TerminatedTreatmentColorectal Cancer / HAI / Hepatic Metastases1
3TerminatedTreatmentColorectal Cancer / Metastatic 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
Injection, powder, lyophilized, for solutionIntra-arterial500 mg/1
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)8.08Chemaxon
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
Polarizability20.95 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-MSsplash10-0036-9340000000-625fd93cccce9bbf8234
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/MSsplash10-000t-1590000000-762be6734bd8d68d445c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4j-0890000000-1fa4908118f46eba831e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000t-9400000000-0c3a7283993c0042cd01
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004l-5930000000-1cf7e2527218d9c2ad84
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0bu0-5920000000-802bb3bed9d13cb26ee8
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002f-7900000000-815996866bde8c30bdb7
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-158.6104097
predicted
DarkChem Lite v0.1.0
[M-H]-158.87955
predicted
DeepCCS 1.0 (2019)
[M+H]+162.2858097
predicted
DarkChem Lite v0.1.0
[M+H]+161.27512
predicted
DeepCCS 1.0 (2019)
[M+Na]+159.0419097
predicted
DarkChem Lite v0.1.0
[M+Na]+167.18782
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Thymidylate synthase
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. [Article]
  2. Kubota T: [Theoretical basis for low-dose CDDP/5-FU therapy]. Gan To Kagaku Ryoho. 1999 Oct;26(11):1536-41. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Details1. Thymidine phosphorylase
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. [Article]
  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. [Article]
Details2. Cytochrome P450 2C9
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. [Article]
  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. [Article]
  3. Gilbar PJ, Brodribb TR: Phenytoin and fluorouracil interaction. Ann Pharmacother. 2001 Nov;35(11):1367-70. doi: 10.1345/aph.1A051. [Article]
  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. [Article]
  5. Up to Date: Floxuridine [Link]

Carriers

Details1. Thyroxine-binding globulin
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 at June 13, 2005 13:24 / Updated at November 03, 2023 23:40