U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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 of TRIFLURIDINE

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
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

Curator's Comment: trifluorothymidine (TFT) does not cross the blood brain barrier

Originator

Curator's Comment: trifluridine, was first synthesized in 1964 by Heidelberger et al.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
VIROPTIC

Approved Use

Unknown

Launch Date

1980
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
96 ng/mL
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
35 mg/m² single, oral
dose: 35 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered: TIPIRACIL
TRIFLURIDINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
248 ng × h/mL
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
35 mg/m² single, oral
dose: 35 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered: TIPIRACIL
TRIFLURIDINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.14 h
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
35 mg/m² single, oral
dose: 35 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered: TIPIRACIL
TRIFLURIDINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4%
unknown, unknown
TRIFLURIDINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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:
unhealthy, 59
Health Status: unhealthy
Age Group: 59
Sex: M+F
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Sources:
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:
unhealthy, 60
Health Status: unhealthy
Age Group: 60
Sex: M+F
Sources:
DLT: Granulocytopenia, Fatigue...
Dose limiting toxicities:
Granulocytopenia (grade 4, 33.3%)
Fatigue (grade 3, 33.3%)
Sources:
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:
unhealthy, 60
Health Status: unhealthy
Age Group: 60
Sex: M+F
Sources:
Other AEs: Granulocytopenia...
Other AEs:
Granulocytopenia (grade 4, 16.7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, 59
Health Status: unhealthy
Age Group: 59
Sex: M+F
Sources:
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:
unhealthy, 60
Health Status: unhealthy
Age Group: 60
Sex: M+F
Sources:
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:
unhealthy, 60
Health Status: unhealthy
Age Group: 60
Sex: M+F
Sources:
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:
unhealthy, 60
Health Status: unhealthy
Age Group: 60
Sex: M+F
Sources:
PubMed

PubMed

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

Sample Use Guides

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
  • Download
Name Type Language
TRIFLURIDINE
INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
NDF-RT N0000175459
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
NDF-RT N0000175459
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
WHO-VATC QS01AD02
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
WHO-ATC L01BC59
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
FDA ORPHAN DRUG 564116
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
NDF-RT N0000175466
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
NDF-RT N0000175459
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
WHO-ATC S01AD02
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
NCI_THESAURUS C1557
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
Code System Code Type Description
ECHA (EC/EINECS)
200-722-8
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
FDA UNII
RMW9V5RW38
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
MESH
D014271
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
RXCUI
10803
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY RxNorm
MESH
C448389
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
RS_ITEM_NUM
1686309
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
PUBCHEM
6256
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
CHEBI
75179
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
DRUG BANK
DB00432
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
WIKIPEDIA
TRIFLURIDINE
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
NSC
75520
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
EPA CompTox
DTXSID4046602
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
IUPHAR
8697
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
NCI_THESAURUS
C905
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
HSDB
8126
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
CAS
70-00-8
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
MERCK INDEX
m11125
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY Merck Index
SMS_ID
100000076935
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
EVMPD
SUB11291MIG
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
DAILYMED
RMW9V5RW38
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
INN
4146
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
NSC
529182
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
DRUG CENTRAL
2743
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
ChEMBL
CHEMBL1129
Created by admin on Wed Apr 02 07:52:40 GMT 2025 , Edited by admin on Wed Apr 02 07:52:40 GMT 2025
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
The in vitro protein binding in human plasma is greater than 96 % for trifluridine.
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE INACTIVE -> PARENT
METABOLITE INACTIVE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE DOSE ADMINISTRATION