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]
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Therapeutic Class

Antiviral Agents

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEBI:75179
CAS Number: 70-00-8
DrugBank ID: DB00432
TTD ID: D05RHI
VARIDT ID: DR00096
INTEDE ID: DR1643

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	[4]

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Thymidine phosphorylase (TYMP)_{Main DME}	DE4HCYL	TYPH_HUMAN	Substrate	[7]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Protein Interaction/Cellular Processes	[8]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Protein Interaction/Cellular Processes	[8]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Protein Interaction/Cellular Processes	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Gene/Protein Processing	[10]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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]	[12]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Trifluridine and Valganciclovir.	Virus infection [1A24-1D9Z]	[12]
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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]	[13]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Trifluridine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[14]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Tecfidera.	Multiple sclerosis [8A40]	[15]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Trifluridine and Siponimod.	Multiple sclerosis [8A40]	[12]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Trifluridine and Fingolimod.	Multiple sclerosis [8A40]	[16]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Ocrelizumab.	Multiple sclerosis [8A40]	[17]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Trifluridine and Ozanimod.	Multiple sclerosis [8A40]	[13]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[18]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Canakinumab.	Rheumatoid arthritis [FA20]	[19]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Rilonacept.	Rheumatoid arthritis [FA20]	[19]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Trifluridine and Golimumab.	Rheumatoid arthritis [FA20]	[20]
Leflunomide	DMR8ONJ	Major	Additive immunosuppressive effects by the combination of Trifluridine and Leflunomide.	Rheumatoid arthritis [FA20]	[14]
Azathioprine	DMMZSXQ	Moderate	Additive immunosuppressive effects by the combination of Trifluridine and Azathioprine.	Transplant rejection [NE84]	[12]
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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	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.
9	Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
10	Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
11	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.
12	Cerner Multum, Inc. "Australian Product Information.".
13	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
15	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
16	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
17	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
18	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
19	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
20	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.