TRIFLURIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H11F3N2O5
Molecular Weight	296.1999
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(C(=O)NC2=O)C(F)(F)F

InChI

InChIKey=VSQQQLOSPVPRAZ-RRKCRQDMSA-N

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

HIDE SMILES / InChI

Molecular Formula	C10H11F3N2O5
Molecular Weight	296.1999
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3a14d86-0ff2-4535-318c-ac8bc8ede42c
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00432 http://www.drugs.com/pro/trifluridine.html

Trifluridine (also called trifluorothymidine or TFT) is an anti-herpesvirus antiviral drug, used primarily on the eye. It was sold under the trade name, Viroptic, by Glaxo Wellcome, now merged into GlaxoSmithKline. It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the -CF3 group added to the uracil component blocks base pairing, thus interfering with DNA replication. It is a component of the experimental anti-cancer drug TAS-102. Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vaccinia virus. Some strains of adenovirus are also inhibited in vitro. VIROPTIC is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, VIROPTIC was also effective. The mechanism of action of trifluridine has not been fully determined, but appears to involve the inhibition of viral replication. Trifluridine does this by incorporating into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2366042 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3a14d86-0ff2-4535-318c-ac8bc8ede42c	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Keratoconjunctivitis 7 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3a14d86-0ff2-4535-318c-ac8bc8ede42c	Curative		Approved 8583	VIROPTIC Approved Use Unknown Launch Date 1980

C_max

Value	Dose	Co-administered	Analyte	Population
96 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		TRIFLURIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
2155 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TIPIRACIL	TIPIRACIL	TRIFLURIDINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
248 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		TRIFLURIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
6694 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TIPIRACIL	TIPIRACIL	TRIFLURIDINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.14 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered:		TRIFLURIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
1.42 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28111727	35 mg/m² single, oral dose: 35 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TIPIRACIL	TIPIRACIL	TRIFLURIDINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207981s008lbl.pdf	unknown, unknown		TRIFLURIDINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
35 mg/m2 2 times / day multiple, oral MTD Dose: 35 mg/m2, 2 times / day Route: oral Route: multiple Dose: 35 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22735906	unhealthy, 59 Health Status: unhealthy Age Group: 59 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22735906	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/22735906
80 mg/m2 3 times / day multiple, oral Highest studied dose Dose: 80 mg/m2, 3 times / day Route: oral Route: multiple Dose: 80 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	DLT: Granulocytopenia, Fatigue... Dose limiting toxicities: Granulocytopenia (grade 4, 33.3%) Fatigue (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/18798063
70 mg/m2 3 times / day multiple, oral MTD Dose: 70 mg/m2, 3 times / day Route: oral Route: multiple Dose: 70 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	Other AEs: Granulocytopenia... Other AEs: Granulocytopenia (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/18798063

AEs

AE	Significance	Dose	Population
Neutropenia	grade 4, 33.3% DLT	35 mg/m2 2 times / day multiple, oral MTD Dose: 35 mg/m2, 2 times / day Route: oral Route: multiple Dose: 35 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22735906	unhealthy, 59 Health Status: unhealthy Age Group: 59 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22735906
Fatigue	grade 3, 33.3% DLT	80 mg/m2 3 times / day multiple, oral Highest studied dose Dose: 80 mg/m2, 3 times / day Route: oral Route: multiple Dose: 80 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18798063
Granulocytopenia	grade 4, 33.3% DLT	80 mg/m2 3 times / day multiple, oral Highest studied dose Dose: 80 mg/m2, 3 times / day Route: oral Route: multiple Dose: 80 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18798063
Granulocytopenia	grade 4, 16.7%	70 mg/m2 3 times / day multiple, oral MTD Dose: 70 mg/m2, 3 times / day Route: oral Route: multiple Dose: 70 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18798063	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18798063

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75179	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75179
eMolecules	1971040	https://www.emolecules.com/cgi-bin/more?vid=1971040
eMolecules	594732	https://www.emolecules.com/cgi-bin/more?vid=594732
MolPort	MolPort-003-959-693	https://www.molport.com/shop/molecule-link/MolPort-003-959-693
Selleck Chemicals	Trifluridine(Viroptic)	http://www.selleckchem.com/products/Trifluridine(Viroptic).html
ZINC	ZINC000003842753	http://zinc15.docking.org/substances/ZINC000003842753

PubMed

Title	Date	PubMed
Cellular and molecular mechanisms for the synergistic cytotoxicity elicited by oxaliplatin and pemetrexed in colon cancer cell lines.	2010-08	20020129
Prodrug activation by Cryptosporidium thymidine kinase.	2010-05-21	20231284
Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells.	2010-05-15	19816940
Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer.	2010-05	20372850
Trifluorothymidine resistance is associated with decreased thymidine kinase and equilibrative nucleoside transporter expression or increased secretory phospholipase A2.	2010-04	20371715
Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines.	2010-02	19886911
A human apolipoprotein E mimetic peptide effectively inhibits HSV-1 TK-positive and TK-negative acute epithelial keratitis in rabbits.	2009-02	19219680
Slitlamp biomicroscopy and photographic image analysis of herpes simplex virus stromal keratitis.	2009-02	19204233
Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent.	2008-11	18957056
Synthesis of nucleoside-based antiviral drugs in ionic liquids.	2008-10-15	18796352
Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors.	2008-10	18798063
Phase 1 study of TAS-102 administered once daily on a 5-day-per-week schedule in patients with solid tumors.	2008-10	18528634
Effective treatment of ocular HSK with a human apolipoprotein E mimetic peptide in a mouse eye model.	2008-10	18515564
[18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study.	2008-08-05	18665170
Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.	2008-07-09	18472234
Trifluorothymidine induces cell death independently of p53.	2008-06	18600528
Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.	2008-02	18201137
Therapeutic interventions for herpes simplex virus epithelial keratitis.	2008-01-23	18254009
Is herpes simplex virus keratitis a different disease in children?	2008-01	18045258
Collision induced dissociation studies of alkali metal adducts of tetracyclines and antiviral agents by electrospray ionization, hydrogen/deuterium exchange and multiple stage mass spectrometry.	2008	19023146
Progressive hypertrophic genital herpes in an HIV-infected woman despite immune recovery on antiretroviral therapy.	2008	18784844
Novel cell death mechanisms of trifluorothymidine.	2008	18776547
Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.	2007-12	19668521
High level glucose increases mutagenesis in human lymphoblastoid cells.	2007-09-04	17848982
Collisionally-induced dissociation of substituted pyrimidine antiviral agents: mechanisms of ion formation using gas phase hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry.	2007-08	17583534
Evidence-based treatment of herpes simplex virus keratitis: a systematic review.	2007-07	17660897
Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment of gastrointestinal malignancies.	2007-06	17441963
Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells.	2007-01-29	17242697
Therapeutic interventions for herpes simplex virus epithelial keratitis.	2007-01-24	17253484
The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells.	2007-01-15	17179993
A method to distinguish between the de novo induction of thymidine kinase mutants and the selection of pre-existing thymidine kinase mutants in the mouse lymphoma assay.	2007-01-10	17055776
Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.	2007-01	17198024
Irinotecan-induced cytotoxicity to colon cancer cells in vitro is stimulated by pre-incubation with trifluorothymidine.	2007-01	17049227
Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors.	2006-09-15	16902987
Microarray analysis distinguishes differential gene expression patterns from large and small colony Thymidine kinase mutants of L5178Y mouse lymphoma cells.	2006-09-06	17118152
Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs.	2006-08-01	16881829
American Society of Clinical Oncology--42nd annual meeting. Poster presentations on leukemia and cytotoxic chemotherapy. 2-6 June 2006, Atlanta, GA, USA.	2006-08	16871453
In vitro comparison of antiviral drugs against feline herpesvirus 1.	2006-04-26	16640781
Imiquimod 5% cream for the treatment of recurrent, acyclovir-resistant genital herpes.	2006-02-15	16421805
3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.	2006-02-15	16290929
Ocular vaccinia infection in laboratory worker, Philadelphia, 2004.	2006-01	16494730
Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells.	2006-01	16010590
Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies.	2006	16489840
Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.	2005-12	16386088
Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis.	2005-11	16227854
Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations.	2005-08-27	16127135
Potentiation of the antitumor activity of alpha, alpha, alpha-trifluorothymidine by the co-administration of an inhibitor of thymidine phosphorylase at a suitable molar ratio in vivo.	2005-08	16010427
Intracellular immunity to HIV-1: newly defined retroviral battles inside infected cells.	2005-04-13	15829012
Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents.	1991-08	1907950
Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine.	1977-07	195058

Patents

Sample Use Guides

In Vivo Use Guide

Instill one drop of VIROPTIC Ophthalmic Solution, 1% onto the cornea of the affected eye every 2 hours while awake for a maximum daily dosage of nine drops until the corneal ulcer has completely re-epithelialized

Route of Administration: Other

In Vitro Use Guide

HeLa cells were treated with Trifluridine (TFT) at a concentration of 1 µM (IC50 value), the concentration of TFT in the DNA was calculated as 62.2±0.9 pmol/1x106 cells for 4 h. Greater degree of incorporation of TFT into the DNA than that of 5FU or FdUrd, and that such a high degree of incorporation of TFT residues into the DNA might be related to exhibit potent cytotoxic activity to be refractory to cleavage by these DNA glycosylases; thus, the DNA-directed cytotoxic effect of the compound is quite different from that of 5FU

Substance Class	Chemical Created by `admin` on `Wed Apr 02 07:52:40 GMT 2025` Edited by `admin` on `Wed Apr 02 07:52:40 GMT 2025`
Record UNII	RMW9V5RW38
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIFLURIDINE

Official Name

English

VIROPTIC

Preferred Name

English

TRIFLURIDINE [USAN]

Common Name

English

F3DTHD

Common Name

English

TRIFLURIDINE [USP-RS]

Common Name

English

TRIFLURIDINE [JAN]

Common Name

English

5-TRIFLUOROMETHYL-2'-DEOXYURIDINE

Systematic Name

English

TRIFLURIDINE [EP MONOGRAPH]

Common Name

English

TRIFLURIDINE [ORANGE BOOK]

Common Name

English

TRIFLURIDINE [USP MONOGRAPH]

Common Name

English

TRIFLURIDINE [MI]

Common Name

English

TRIFLUOROTHYMIDINE

Systematic Name

English

TRIFLUOROMETHYLDEOXYURIDINE

Systematic Name

English

trifluridine [INN]

Common Name

English

2'-DEOXY-5-(TRIFLUOROMETHYL)URIDINE

Systematic Name

English

THYMIDINE, .ALPHA.,.ALPHA.,.ALPHA.-TRIFLUORO-

Systematic Name

English

TRIFLURIDINE [VANDF]

Common Name

English

S-95005 COMPONENT TRIFLURIDINE

Common Name

English

NSC-75520

Code

English

TRIFLURIDINE [MART.]

Common Name

English

NSC-529182

Code

English

F3T

Common Name

English

Trifluridine [WHO-DD]

Common Name

English

TAS-102 COMPONENT TRIFLURIDINE

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175595