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

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
Interventions for herpes simplex virus epithelial keratitis.
2001
In vitro effects of antiviral agents on human keratocytes.
2001 Jan
Mutation induction in human cells after low dose X ray exposure.
2002
Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans.
2003 Aug 4
Detection of thymidylate synthase modulators by a novel screening assay.
2003 Jan
Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity.
2003 Mar 24
Comparison of HSV-1 thymidine kinase-dependent and -independent inhibition of replication-competent adenoviral vectors by a panel of drugs.
2003 Oct
Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
2003 Sep 15
Arthrographis keratitis mimicking acanthamoeba keratitis.
2004 Apr
Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model.
2004 Feb
Pharmacokinetic modeling of species-dependent enhanced bioavailability of trifluorothymidine by thymidine phosphorylase inhibitor.
2004 Jun
[The latest in herpes simplex keratitis therapy].
2004 May
A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA.
2004 Sep
Intracellular immunity to HIV-1: newly defined retroviral battles inside infected cells.
2005 Apr 13
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
American Society of Clinical Oncology--42nd annual meeting. Poster presentations on leukemia and cytotoxic chemotherapy. 2-6 June 2006, Atlanta, GA, USA.
2006 Aug
Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.
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
Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment of gastrointestinal malignancies.
2007 Jun
Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.
2008 Feb
Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors.
2008 Oct
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
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
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