U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H11F3N2O5
Molecular Weight 296.2003
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIFLURIDINE

SMILES

C1[C@@]([H])([C@@]([H])(CO)O[C@@]1([H])n2cc(c(nc2=O)O)C(F)(F)F)O

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 296.2003
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

3.39465601E11
Cmax

Cmax

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

AUC

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

Funbound

ValueDoseCo-administeredAnalytePopulation
6%
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
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.431, 432
unhealthy, 59
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 59
Sex: M+F
Population Size: 3
Sources: Page: p.431, 432
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Sources: Page: p.431, 432
80 mg/m2 3 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 80 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg/m2, 3 times / day
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.797
unhealthy, 60
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 60
Sex: M+F
Population Size: 6
Sources: Page: p.797
DLT: Granulocytopenia, Fatigue...
Dose limiting toxicities:
Granulocytopenia (grade 4, 33.3%)
Fatigue (grade 3, 33.3%)
Sources: Page: p.797
70 mg/m2 3 times / day multiple, oral (total daily dose)
MTD
Dose: 70 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 70 mg/m2, 3 times / day
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.797
unhealthy, 60
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 60
Sex: M+F
Population Size: 6
Sources: Page: p.797
Other AEs: Granulocytopenia...
Other AEs:
Granulocytopenia (grade 4, 16.7%)
Sources: Page: p.797
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
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.431, 432
unhealthy, 59
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 59
Sex: M+F
Population Size: 3
Sources: Page: p.431, 432
Fatigue grade 3, 33.3%
DLT
80 mg/m2 3 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 80 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg/m2, 3 times / day
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.797
unhealthy, 60
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 60
Sex: M+F
Population Size: 6
Sources: Page: p.797
Granulocytopenia grade 4, 33.3%
DLT
80 mg/m2 3 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 80 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg/m2, 3 times / day
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.797
unhealthy, 60
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 60
Sex: M+F
Population Size: 6
Sources: Page: p.797
Granulocytopenia grade 4, 16.7%
70 mg/m2 3 times / day multiple, oral (total daily dose)
MTD
Dose: 70 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 70 mg/m2, 3 times / day
Co-administed with::
thymidine phosphorylase, p.o
Sources: Page: p.797
unhealthy, 60
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 60
Sex: M+F
Population Size: 6
Sources: Page: p.797
PubMed

PubMed

TitleDatePubMed
Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine.
1977 Jul
Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents.
1991 Aug
Intracellular immunity to HIV-1: newly defined retroviral battles inside infected cells.
2005 Apr 13
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
3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.
2006 Feb 15
Ocular vaccinia infection in laboratory worker, Philadelphia, 2004.
2006 Jan
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
Microarray analysis distinguishes differential gene expression patterns from large and small colony Thymidine kinase mutants of L5178Y mouse lymphoma cells.
2006 Sep 6
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 Aug
Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.
2007 Dec
Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.
2007 Jan
Irinotecan-induced cytotoxicity to colon cancer cells in vitro is stimulated by pre-incubation with trifluorothymidine.
2007 Jan
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 Jan 10
The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells.
2007 Jan 15
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
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
Progressive hypertrophic genital herpes in an HIV-infected woman despite immune recovery on antiretroviral therapy.
2008
Novel cell death mechanisms of trifluorothymidine.
2008
[18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study.
2008 Aug 5
Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.
2008 Feb
Is herpes simplex virus keratitis a different disease in children?
2008 Jan
Therapeutic interventions for herpes simplex virus epithelial keratitis.
2008 Jan 23
Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.
2008 Jul 9
Trifluorothymidine induces cell death independently of p53.
2008 Jun
Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent.
2008 Nov
Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors.
2008 Oct
Phase 1 study of TAS-102 administered once daily on a 5-day-per-week schedule in patients with solid tumors.
2008 Oct
Effective treatment of ocular HSK with a human apolipoprotein E mimetic peptide in a mouse eye model.
2008 Oct
Synthesis of nucleoside-based antiviral drugs in ionic liquids.
2008 Oct 15
A human apolipoprotein E mimetic peptide effectively inhibits HSV-1 TK-positive and TK-negative acute epithelial keratitis in rabbits.
2009 Feb
Slitlamp biomicroscopy and photographic image analysis of herpes simplex virus stromal keratitis.
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
Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines.
2010 Feb
Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer.
2010 May
Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells.
2010 May 15
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 Fri Jun 25 20:58:50 UTC 2021
Edited
by admin
on Fri Jun 25 20:58:50 UTC 2021
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
TRIFLURIDINE [USAN]
Common Name English
F3DTHD
Common Name English
TRIFLURIDINE [USP-RS]
Common Name English
5-TRIFLUOROMETHYL-2'-DEOXYURIDINE
Systematic Name English
TRIFLURIDINE [EP MONOGRAPH]
Common Name English
TRIFLURIDINE [WHO-DD]
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
TRIFLURIDINE COMPONENT OF LONSURF
Brand Name English
NSC-75520
Code English
TRIFLURIDINE [MART.]
Common Name English
NSC-529182
Code English
F3T
Common Name English
VIROPTIC
Brand Name English
Classification Tree Code System Code
NDF-RT N0000175595
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
WHO-VATC QS01AD02
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
WHO-ATC L01BC59
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
NDF-RT N0000175466
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
FDA ORPHAN DRUG 564116
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
WHO-ATC S01AD02
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
NCI_THESAURUS C1557
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
200-722-8
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
FDA UNII
RMW9V5RW38
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
MESH
D014271
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
RXCUI
10803
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY RxNorm
MESH
C448389
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
PUBCHEM
6256
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
USP_CATALOG
1686309
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB00432
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
WIKIPEDIA
TRIFLURIDINE
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
EPA CompTox
70-00-8
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
IUPHAR
8697
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
NCI_THESAURUS
C905
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
HSDB
8126
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
CAS
70-00-8
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
MERCK INDEX
M11125
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY Merck Index
EVMPD
SUB11291MIG
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
INN
4146
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
DRUG CENTRAL
2743
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
PRIMARY
ChEMBL
CHEMBL1129
Created by admin on Fri Jun 25 20:58:50 UTC 2021 , Edited by admin on Fri Jun 25 20:58:50 UTC 2021
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