Details of the Drug

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]

Affected Organisms

Humans and other mammals

ATC Code

L01BC09: Floxuridine

L01BC: Pyrimidine analogues

L01B: ANTIMETABOLITES

L01: ANTINEOPLASTIC AGENTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEMBL917
CAS Number: 50-91-9
UNII: 039LU44I5M
DrugBank ID: DB00322
TTD ID: D0TS1Z
VARIDT ID: DR00682
INTEDE ID: DR1754

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Drug Response	[8]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Drug Response	[9]
DNA repair protein XRCC1	OTWRV4S2	XRCC1_HUMAN	Drug Response	[10]
DNA repair protein XRCC4	OT4SXOIZ	XRCC4_HUMAN	Drug Response	[11]
Metalloproteinase inhibitor 3 (TIMP3)	OTDGQAD1	TIMP3_HUMAN	Drug Response	[12]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Drug Response	[10]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Gene/Protein Processing	[13]
Thymidine kinase, cytosolic (TK1)	OTY5JFM1	KITH_HUMAN	Gene/Protein Processing	[14]
Thymidylate synthase	OTXTG0C7	TYSY_HUMAN	Drug Response	[15]

Molecular Interaction Atlas (MIA)

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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]	[16]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Ciprofloxacin XR	DM2NLS9	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Ciprofloxacin XR.	Bacterial infection [1A00-1C4Z]	[17]
Trovafloxacin	DM6AN32	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Trovafloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[17]
ABT-492	DMJFD2I	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[17]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Lomefloxacin	DMVRH9C	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Grepafloxacin	DMGLX0T	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Grepafloxacin.	Bronchitis [CA20]	[17]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Floxuridine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[18]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Floxuridine and Denosumab.	Low bone mass disorder [FB83]	[19]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Floxuridine and Thalidomide.	Multiple myeloma [2A83]	[20]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Floxuridine and Tecfidera.	Multiple sclerosis [8A40]	[21]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Floxuridine and Siponimod.	Multiple sclerosis [8A40]	[22]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Floxuridine and Fingolimod.	Multiple sclerosis [8A40]	[23]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Floxuridine and Ocrelizumab.	Multiple sclerosis [8A40]	[24]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Floxuridine and Ozanimod.	Multiple sclerosis [8A40]	[16]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Floxuridine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[25]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[17]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Floxuridine and Canakinumab.	Rheumatoid arthritis [FA20]	[26]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Floxuridine and Rilonacept.	Rheumatoid arthritis [FA20]	[26]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Floxuridine and Golimumab.	Rheumatoid arthritis [FA20]	[27]
Leflunomide	DMR8ONJ	Major	Additive immunosuppressive effects by the combination of Floxuridine and Leflunomide.	Rheumatoid arthritis [FA20]	[18]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Floxuridine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[28]
Azathioprine	DMMZSXQ	Moderate	Additive myelosuppressive effects by the combination of Floxuridine and Azathioprine.	Transplant rejection [NE84]	[22]
Cinoxacin	DM4EWNS	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Cinoxacin.	Urinary tract infection [GC08]	[17]
Nalidixic acid	DMRM0JV	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Nalidixic acid.	Urinary tract infection [GC08]	[17]
Enoxacin	DMYTE6L	Minor	Decreased absorption of Floxuridine due to intestinal mucosa variation caused by Enoxacin.	Urinary tract infection [GC08]	[17]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Floxuridine and Ganciclovir.	Virus infection [1A24-1D9Z]	[22]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Floxuridine and Valganciclovir.	Virus infection [1A24-1D9Z]	[22]


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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	[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.
9	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.
10	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.
11	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.
12	DNA methylation and sensitivity to antimetabolites in cancer cell lines. Oncol Rep. 2008 Feb;19(2):407-12.
13	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.
14	Fluorodeoxyuridine modulates cellular expression of the DNA base excision repair enzyme uracil-DNA glycosylase. Cancer Res. 2006 Sep 1;66(17):8829-37. doi: 10.1158/0008-5472.CAN-06-0540.
15	Thymidylate synthetase mRNA levels are increased in liver metastases of colorectal cancer patients resistant to fluoropyrimidine-based chemotherapy. BMC Cancer. 2004 Mar 25;4:11. doi: 10.1186/1471-2407-4-11.
16	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
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18	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
19	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
20	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]
21	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
22	Cerner Multum, Inc. "Australian Product Information.".
23	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
24	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
25	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
26	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
27	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
28	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]