General Information of Drug (ID: DM04LR2)

Drug Name
Floxuridine
Synonyms
floxuridine; 50-91-9; 2'-Deoxy-5-fluorouridine; 5-Fluorodeoxyuridine; Fluorodeoxyuridine; Floxuridin; FUDR; Fluoruridine deoxyribose; Deoxyfluorouridine; 5-Fluoro-2'-deoxyuridine; FdUrd; Floxuridinum; Floxiridina; 5FdU; 5-fluoro-1-((2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1h,3h)-dione; 5-Fluoro-2-desoxyuridine; 5 Fluorodeoxyuridine; Floxuridinum [INN-Latin]; FDUR; Floxiridina [INN-Spanish]; beta-5-Fluoro-2'-deoxyuridine; 5-Fluoro-2-deoxyuridine; 5-FdUrd; 5-Fluorouracil deoxyriboside; Sterile fudr (TN); Floxuridine/5-fluorouracil
Indication
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Approved [1]
Liver cancer 2C12 Approved [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Colon cancer 2B90.Z Investigative [2]
Gastric cancer 2B72 Investigative [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 246.19
Logarithm of the Partition Coefficient (xlogp) -1.2
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Bioavailability
90% of drug becomes completely available to its intended biological destination(s) [4]
Metabolism
The drug is metabolized via the hepatic []
Chemical Identifiers
Formula
C9H11FN2O5
IUPAC Name
5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
Canonical SMILES
C1[C@@H]([C@H](O[C@H]1N2C=C(C(=O)NC2=O)F)CO)O
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
InChIKey
ODKNJVUHOIMIIZ-RRKCRQDMSA-N
Cross-matching ID
PubChem CID
5790
ChEBI ID
CHEBI:60761
CAS Number
50-91-9
DrugBank ID
DB00322
TTD ID
D0TS1Z
VARIDT ID
DR00682
INTEDE ID
DR1754
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Thymidine phosphorylase (TYMP)
Main DME
DE4HCYL TYPH_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
C-1-tetrahydrofolate synthase, cytoplasmic (MTHFD1) OTMKHVWC C1TC_HUMAN Drug Response [7]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [8]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP) OTPYQX3K C1QBP_HUMAN Drug Response [9]
Dihydrofolate reductase (DHFR) OT3DVIGM DYR_HUMAN Drug Response [7]
DNA mismatch repair protein Mlh1 (MLH1) OTG5XDD8 MLH1_HUMAN Drug Response [10]
DNA mismatch repair protein Msh2 (MSH2) OT10H1AB MSH2_HUMAN Drug Response [10]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Drug Response [11]
DNA repair protein XRCC1 OTWRV4S2 XRCC1_HUMAN Drug Response [12]
DNA repair protein XRCC4 OT4SXOIZ XRCC4_HUMAN Drug Response [13]
Folate receptor alpha (FOLR1) OT0QZ0H6 FOLR1_HUMAN Drug Response [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Floxuridine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Floxuridine and Roflumilast. Asthma [CA23] [14]
Ofloxacin DM0VQN3 Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Ofloxacin. Bacterial infection [1A00-1C4Z] [15]
Ciprofloxacin XR DM2NLS9 Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Ciprofloxacin XR. Bacterial infection [1A00-1C4Z] [15]
Trovafloxacin DM6AN32 Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Trovafloxacin. Bacterial infection [1A00-1C4Z] [15]
Sparfloxacin DMB4HCT Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Sparfloxacin. Bacterial infection [1A00-1C4Z] [15]
Gemifloxacin DMHT34O Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Gemifloxacin. Bacterial infection [1A00-1C4Z] [15]
Norfloxacin DMIZ6W2 Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Norfloxacin. Bacterial infection [1A00-1C4Z] [15]
ABT-492 DMJFD2I Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [15]
Levofloxacin DMS60RB Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Levofloxacin. Bacterial infection [1A00-1C4Z] [15]
Lomefloxacin DMVRH9C Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Lomefloxacin. Bacterial infection [1A00-1C4Z] [15]
Grepafloxacin DMGLX0T Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Grepafloxacin. Bronchitis [CA20] [15]
Teriflunomide DMQ2FKJ Major Additive immunosuppressive effects by the combination of Floxuridine and Teriflunomide. Hyper-lipoproteinaemia [5C80] [16]
Denosumab DMNI0KO Moderate Additive immunosuppressive effects by the combination of Floxuridine and Denosumab. Low bone mass disorder [FB83] [17]
Thalidomide DM70BU5 Major Additive thrombogenic effects by the combination of Floxuridine and Thalidomide. Multiple myeloma [2A83] [18]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Floxuridine and Tecfidera. Multiple sclerosis [8A40] [19]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Floxuridine and Siponimod. Multiple sclerosis [8A40] [20]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Floxuridine and Fingolimod. Multiple sclerosis [8A40] [21]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Floxuridine and Ocrelizumab. Multiple sclerosis [8A40] [22]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Floxuridine and Ozanimod. Multiple sclerosis [8A40] [14]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive myelosuppressive effects by the combination of Floxuridine and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [23]
Gatifloxacin DMSL679 Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Gatifloxacin. Respiratory infection [CA07-CA4Z] [15]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Floxuridine and Canakinumab. Rheumatoid arthritis [FA20] [24]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Floxuridine and Rilonacept. Rheumatoid arthritis [FA20] [24]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Floxuridine and Golimumab. Rheumatoid arthritis [FA20] [25]
Leflunomide DMR8ONJ Major Additive immunosuppressive effects by the combination of Floxuridine and Leflunomide. Rheumatoid arthritis [FA20] [16]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Floxuridine when combined with Anthrax vaccine. Sepsis [1G40-1G41] [26]
Azathioprine DMMZSXQ Moderate Additive myelosuppressive effects by the combination of Floxuridine and Azathioprine. Transplant rejection [NE84] [20]
Cinoxacin DM4EWNS Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Cinoxacin. Urinary tract infection [GC08] [15]
Nalidixic acid DMRM0JV Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Nalidixic acid. Urinary tract infection [GC08] [15]
Enoxacin DMYTE6L Minor Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Enoxacin. Urinary tract infection [GC08] [15]
Ganciclovir DM1MBYQ Moderate Additive myelosuppressive effects by the combination of Floxuridine and Ganciclovir. Virus infection [1A24-1D9Z] [20]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Floxuridine and Valganciclovir. Virus infection [1A24-1D9Z] [20]
⏷ Show the Full List of 32 DDI Information of This Drug

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 Floxuridine FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4801).
4 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5 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.
6 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.
7 Folic Acid-Metabolizing Enzymes Regulate the Antitumor Effect of 5-Fluoro-2'-Deoxyuridine in Colorectal Cancer Cell Lines. PLoS One. 2016 Sep 29;11(9):e0163961. doi: 10.1371/journal.pone.0163961. eCollection 2016.
8 Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
9 [Expression of C1QBP gene and its correlation with drug resistance in human resistance choriocarcinoma cell line]. Zhonghua Fu Chan Ke Za Zhi. 2014 Aug;49(8):616-20.
10 Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil. PLoS One. 2011;6(12):e28862. doi: 10.1371/journal.pone.0028862. Epub 2011 Dec 15.
11 Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res. 2009 Jun;7(6):897-906. doi: 10.1158/1541-7786.MCR-08-0519. Epub 2009 May 26.
12 Poly(ADP-Ribose) polymerase inhibition synergizes with 5-fluorodeoxyuridine but not 5-fluorouracil in ovarian cancer cells. Cancer Res. 2011 Jul 15;71(14):4944-54. doi: 10.1158/0008-5472.CAN-11-0814. Epub 2011 May 25.
13 Differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells. J Radiat Res. 2011;52(4):415-24. doi: 10.1269/jrr.10168.
14 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
16 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
17 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
18 Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
19 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
20 Cerner Multum, Inc. "Australian Product Information.".
21 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
22 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
23 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
24 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
25 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
26 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]