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Identification
Name Floxuridine
Accession Number DB00322 (APRD00692)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
5 Fluorodeoxyuridine
5FDU
Deoxyfluorouridine
FDUR
FDURD
Floxiridina [INN-Spanish]
Floxuridin
Floxuridinum [INN-Latin]
Fluorodeoxyuridine
Fluoruridine Deoxyribose
Salts Not Available
Brand names
Name Company
FUDR
Brand mixtures Not Available
Categories
  • Antimetabolites
  • Antineoplastics
  • Antimetabolites, Antineoplastic
CAS number 50-91-9
Weight Average: 246.1924
Monoisotopic: 246.065199677
Chemical Formula C9H11FN2O5
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec show (9.43 KB)
Taxonomy
Kingdom Organic
Classes
  • Glycerol and Derivatives
  • Pyrimidines and Derivatives
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Furans
  • Cyanamides
  • Aryl Halides
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).
Pharmacodynamics Floxuridine 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 action Floxuridine 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Hepatic.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Floxuridine
5-fluorouracil Details
Floxuridine
    		Dihydrofluorouracil Details
    Floxuridine
      		alpha-Fluoro-beta-alanine Details
      Floxuridine
        		Fluoro-beta-ureidopropionate Details
        Route of elimination The 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 life Not Available
        Clearance Not Available
        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
        Pharmacoeconomics
        Manufacturers
        • App pharmaceuticals llc
        • Bedford laboratories div ben venue laboratories inc
        • Hospira inc
        Packagers
        Dosage forms
        Form Route Strength
        Powder, for solution Intra-arterial
        Prices
        Unit description Cost Unit
        Floxuridine 500 mg vial 144.0 USD vial
        Fudr 500 mg vial 121.06 USD vial
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents Not Available
        Properties
        State solid
        Experimental Properties
        Property Value Source
        melting point 150.5 °C PhysProp
        water solubility 1.19E+004 mg/L Not Available
        logP -1.16 HANSCH,C ET AL. (1995)
        pKa 7.44 SANGSTER (1994)
        Predicted Properties
        Property Value Source
        water solubility 4.08e+01 g/l ALOGPS
        logP -1.1 ALOGPS
        logP -1.3 ChemAxon
        logS -0.78 ALOGPS
        pKa (strongest acidic) 7.68 ChemAxon
        pKa (strongest basic) -3 ChemAxon
        physiological charge 0 ChemAxon
        hydrogen acceptor count 5 ChemAxon
        hydrogen donor count 3 ChemAxon
        polar surface area 99.1 ChemAxon
        rotatable bond count 2 ChemAxon
        refractivity 51.26 ChemAxon
        polarizability 20.78 ChemAxon
        References
        Synthesis Reference Not Available
        General Reference Not Available
        External Links
        Resource Link
        KEGG Drug D04197 Link_out
        KEGG Compound C11736 Link_out
        PubChem Compound 5790 Link_out
        PubChem Substance 46508645 Link_out
        ChemSpider 5586 Link_out
        BindingDB 50042595 Link_out
        ChEBI 60761 Link_out
        ChEMBL 60761 Link_out
        Therapeutic Targets Database DAP001245 Link_out
        PharmGKB PA449652 Link_out
        RxList http://www.rxlist.com/cgi/generic2/floxuridine.htm Link_out
        Drugs.com http://www.drugs.com/cdi/floxuridine.html Link_out
        Wikipedia http://en.wikipedia.org/wiki/Floxuridine Link_out
        ATC Codes Not Available
        AHFS Codes Not Available
        PDB Entries Not Available
        FDA label Not Available
        MSDS show (40.5 KB)
        Interactions
        Drug Interactions
        Drug Interaction
        Tamoxifen Floxuridine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Floxiridine is initiated, discontinued or dose changed.
        Tolbutamide Floxuridine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Floxuridine is initiated, discontinued or dose changed.
        Torasemide Floxuridine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Floxuridine is initiated, discontinued or dose changed.
        Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
        Trimethoprim The strong CYP2C9 inhibitor, Floxuridine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Floxuridine is initiated, discontinued or dose changed.
        Voriconazole Floxuridine, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if floxuridine is initiated, discontinued or dose changed.
        Warfarin Floxuridine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if floxuridine is initiated, discontinued or dose changed.
        Zafirlukast Floxuridine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if floxuridine is initiated, discontinued or dose changed.
        Food Interactions Not Available
        Targets

        1. Thymidylate synthase

        Pharmacological action: yes
        Organism class: human
        UniProt ID: P04818 Link_out
        Gene: TYMS Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        SNPs: SNPJam Report Link_out

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

        1. Thymidine phosphorylase

        Actions: substrate

        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

        UniProt ID: P19971 Link_out
        Gene: ECGF1 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        SNPs: SNPJam Report Link_out

        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
        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
        Comments
        Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19