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
Synthesis and in vitro activity of D- and L-enantiomers of 5-(trifluoromethyl)uracil nucleoside derivatives.	2001 Apr-Jul	11562969
Antiviral drugs: current state of the art.	2001 Aug	11418355
Influence of radiation sterilization on the stability of trifluorothymidine.	2001 Jul 17	11427351
Atypical presentation of Acanthamoeba keratitis.	2001 Oct	11588431
Drugs for non-HIV viral infections.	2002 Feb 4	11828264
Interventions for herpes simplex virus epithelial keratitis.	2003	12917935
Management of acyclovir-resistant herpes simplex virus.	2003 Apr	12757254
Ocular complications of smallpox vaccination.	2003 Aug	12888060
Recurrence of keratitis after excimer laser keratectomy.	2003 Jan	12551688
Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion, antiviral activity and transport across rabbit cornea.	2003 Mar-Apr	12815543
Design of Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors.	2003 May-Aug	14565282
[Trifluridine therapy in herpetic in keratitis].	2004 Apr-Jun	15688823
Ocular vaccinia following exposure to a smallpox vaccinee.	2004 Mar	15013881
The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase.	2004 May 3	15140625
Role of platelet derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity and potential role of deoxyribose-1-phosphate.	2004 Oct	15571282
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 Aug	16010427
Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations.	2005 Aug 27	16127135
Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.	2005 Dec	16386088
Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis.	2005 Nov	16227854
Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies.	2006	16489840
In vitro comparison of antiviral drugs against feline herpesvirus 1.	2006 Apr 26	16640781
American Society of Clinical Oncology--42nd annual meeting. Poster presentations on leukemia and cytotoxic chemotherapy. 2-6 June 2006, Atlanta, GA, USA.	2006 Aug	16871453
Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs.	2006 Aug 1	16881829
Imiquimod 5% cream for the treatment of recurrent, acyclovir-resistant genital herpes.	2006 Feb 15	16421805
Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells.	2006 Jan	16010590
Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors.	2006 Sep 15	16902987
Irinotecan-induced cytotoxicity to colon cancer cells in vitro is stimulated by pre-incubation with trifluorothymidine.	2007 Jan	17049227
Therapeutic interventions for herpes simplex virus epithelial keratitis.	2007 Jan 24	17253484
Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells.	2007 Jan 29	17242697
Evidence-based treatment of herpes simplex virus keratitis: a systematic review.	2007 Jul	17660897
Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment of gastrointestinal malignancies.	2007 Jun	17441963
High level glucose increases mutagenesis in human lymphoblastoid cells.	2007 Sep 4	17848982
Therapeutic interventions for herpes simplex virus epithelial keratitis.	2008 Jan 23	18254009
Trifluorothymidine induces cell death independently of p53.	2008 Jun	18600528
A human apolipoprotein E mimetic peptide effectively inhibits HSV-1 TK-positive and TK-negative acute epithelial keratitis in rabbits.	2009 Feb	19219680
Trifluorothymidine resistance is associated with decreased thymidine kinase and equilibrative nucleoside transporter expression or increased secretory phospholipase A2.	2010 Apr	20371715
Cellular and molecular mechanisms for the synergistic cytotoxicity elicited by oxaliplatin and pemetrexed in colon cancer cell lines.	2010 Aug	20020129
Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer.	2010 May	20372850
Prodrug activation by Cryptosporidium thymidine kinase.	2010 May 21	20231284

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