Details of the Drug

General Information of Drug (ID: DMG2YBD)

Drug Name
Trifluridine
Synonyms
Fluridine; TFDU; TRIFLUOROTHYMIDINE; Trifluoridine; Trifluoromethyldeoxyuridine; Trifluridina; Trifluridinum; Virophta; Viroptic; Trifluorothymine deoxyriboside; CF3dUrd; F3DThd; F3T; F3TDR; HS-0007; Trifluridina [INN-Spanish]; Trifluridine [USAN:INN]; Trifluridinum [INN-Latin]; Viroptic (TN); Trifluridine (USP/INN);Viroptic, Trifluorothymidine, Trifluridine; Alpha,alpha,alpha-Trifluorothymidine; 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione; 2'-Deoxy-5-(trifluoromethyl)uridine; 2'-Deoxy-5-trifluoromethyluridine; 5-(Trifluoromethyl)-2'-deoxyuridine; 5-(Trifluoromethyl)deoxyuridine; 5-Trifluoro-2'-deoxythymidine; 5-Trifluoromethyl-2'-deoxyuridine; 5-Trifluoromethyl-2-deoxyuridine; 5-Trifluorothymidine
Indication
Disease Entry ICD 11 Status REF
Herpetic keratitis 1F00.10 Approved [1]
Virus infection 1A24-1D9Z Approved [2]
Colon cancer 2B90.Z Investigative [1]
Therapeutic Class
Antiviral Agents
Affected Organisms
Human Herpes Virus
ATC Code
S01AD02: Trifluridine
S01AD: Antivirals
S01A: ANTIINFECTIVES
S01: OPHTHALMOLOGICALS
S: SENSORY ORGANS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 296.2
Logarithm of the Partition Coefficient (xlogp) -0.5
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Clearance
The apparent oral clearance of drug is 10.5 L/h []
Elimination
About 55% of the total recovered radio-labelled trifluridine was detected in the urine within 24 hours []
Half-life
The concentration or amount of drug in body reduced by one-half in 12 - 18 minutes []
Metabolism
The drug is metabolized via thymidine phosphorylase (TPase) to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY) [3]
Vd
The volume of distribution (Vd) of drug is 21 L []
Chemical Identifiers
Formula
C10H11F3N2O5
IUPAC Name
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione
Canonical SMILES
C1[C@@H]([C@H](O[C@H]1N2C=C(C(=O)NC2=O)C(F)(F)F)CO)O
InChI
InChI=1S/C10H11F3N2O5/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7/h2,5-7,16-17H,1,3H2,(H,14,18,19)/t5-,6+,7+/m0/s1
InChIKey
VSQQQLOSPVPRAZ-RRKCRQDMSA-N
Cross-matching ID
PubChem CID
6256
ChEBI ID
CHEMBL1129
CAS Number
70-00-8
UNII
RMW9V5RW38
DrugBank ID
DB00432
TTD ID
D05RHI
VARIDT ID
DR00096
INTEDE ID
DR1643
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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 [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [5]
Concentrative nucleoside transporter 1 (SLC28A1) DT0EQPW S28A1_HUMAN Substrate [5]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [5]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Thymidine phosphorylase (TYMP)
Main DME 		DE4HCYL TYPH_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Gene/Protein Processing [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [9]
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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Trifluridine
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Ganciclovir DM1MBYQ Moderate Additive myelosuppressive effects by the combination of Trifluridine and Ganciclovir. Virus infection [1A24-1D9Z] [10]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Trifluridine and Valganciclovir. Virus infection [1A24-1D9Z] [10]
Coadministration of a Drug Treating the Disease Different from Trifluridine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Trifluridine and Roflumilast. Asthma [CA23] [11]
Teriflunomide DMQ2FKJ Major Additive immunosuppressive effects by the combination of Trifluridine and Teriflunomide. Hyper-lipoproteinaemia [5C80] [12]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Trifluridine and Tecfidera. Multiple sclerosis [8A40] [13]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Trifluridine and Siponimod. Multiple sclerosis [8A40] [10]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Trifluridine and Fingolimod. Multiple sclerosis [8A40] [14]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Trifluridine and Ocrelizumab. Multiple sclerosis [8A40] [15]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Trifluridine and Ozanimod. Multiple sclerosis [8A40] [11]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Trifluridine and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [16]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Trifluridine and Canakinumab. Rheumatoid arthritis [FA20] [17]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Trifluridine and Rilonacept. Rheumatoid arthritis [FA20] [17]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Trifluridine and Golimumab. Rheumatoid arthritis [FA20] [18]
Leflunomide DMR8ONJ Major Additive immunosuppressive effects by the combination of Trifluridine and Leflunomide. Rheumatoid arthritis [FA20] [12]
Azathioprine DMMZSXQ Moderate Additive immunosuppressive effects by the combination of Trifluridine and Azathioprine. Transplant rejection [NE84] [10]
⏷ Show the Full List of 13 DDI Information of This Drug

References

1 Trifluridine FDA Label
2 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: 8697).
3 Mogalian E, German P, Kearney BP, Yang CY, Brainard D, Link J, McNally J, Han L, Ling J, Mathias A: Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02084-16. doi: 10.1128/AAC.02084-16. Print 2017 May.
4 Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
5 Lonsurf, INN-trifluridine/tipiracil.
6 Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9.
7 Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9.
8 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
9 Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer. 2010 May 15;126(10):2457-68. doi: 10.1002/ijc.24943.
10 Cerner Multum, Inc. "Australian Product Information.".
11 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
12 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
13 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
14 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
15 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
16 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
17 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
18 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.