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
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
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 |
DescriptionSources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3a14d86-0ff2-4535-318c-ac8bc8ede42cCurator's Comment: description was created based on several sources, including:
http://www.drugbank.ca/drugs/DB00432
http://www.drugs.com/pro/trifluridine.html
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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/3020165
Curator's Comment: trifluorothymidine (TFT) does not cross the blood brain barrier
Originator
Sources: http://www.medkoo.com/products/5884
Curator's Comment: trifluridine, was first synthesized in 1964 by Heidelberger et al.
Approval Year
Cmax
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 |
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 |
TRIFLURIDINE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
T1/2
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 |
TRIFLURIDINE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4% |
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: |
unhealthy, 59 |
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 |
DLT: Granulocytopenia, Fatigue... Dose limiting toxicities: Granulocytopenia (grade 4, 33.3%) Sources: Fatigue (grade 3, 33.3%) |
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 |
Other AEs: Granulocytopenia... |
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: |
unhealthy, 59 |
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 |
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 |
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 |
PubMed
Title | Date | PubMed |
---|---|---|
Synthesis and in vitro activity of D- and L-enantiomers of 5-(trifluoromethyl)uracil nucleoside derivatives. | 2001 Apr-Jul |
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Antiviral drugs: current state of the art. | 2001 Aug |
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Influence of radiation sterilization on the stability of trifluorothymidine. | 2001 Jul 17 |
|
Atypical presentation of Acanthamoeba keratitis. | 2001 Oct |
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Drugs for non-HIV viral infections. | 2002 Feb 4 |
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Interventions for herpes simplex virus epithelial keratitis. | 2003 |
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Management of acyclovir-resistant herpes simplex virus. | 2003 Apr |
|
Ocular complications of smallpox vaccination. | 2003 Aug |
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Recurrence of keratitis after excimer laser keratectomy. | 2003 Jan |
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Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion, antiviral activity and transport across rabbit cornea. | 2003 Mar-Apr |
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Design of Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors. | 2003 May-Aug |
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[Trifluridine therapy in herpetic in keratitis]. | 2004 Apr-Jun |
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Ocular vaccinia following exposure to a smallpox vaccinee. | 2004 Mar |
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The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase. | 2004 May 3 |
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Role of platelet derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity and potential role of deoxyribose-1-phosphate. | 2004 Oct |
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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 |
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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 |
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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 |
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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 |
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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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/21491084
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
Edited
Wed Apr 02 07:52:40 GMT 2025
by
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on
Wed Apr 02 07:52:40 GMT 2025
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Record UNII |
RMW9V5RW38
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175595
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NDF-RT |
N0000175459
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N0000175459
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QS01AD02
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WHO-ATC |
L01BC59
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FDA ORPHAN DRUG |
564116
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N0000175466
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N0000175459
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S01AD02
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NCI_THESAURUS |
C1557
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C448389
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DB00432
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TRIFLURIDINE
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Related Record | Type | Details | ||
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EXCRETED UNCHANGED |
URINE
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BINDER->LIGAND |
The in vitro protein binding in human plasma is greater than 96 % for trifluridine.
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TARGET -> INHIBITOR |
Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT |
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE -> PARENT |
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IMPURITY -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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SINGLE DOSE ADMINISTRATION |
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