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
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 |
---|---|---|---|---|
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 |
|
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 blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 |
|
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 blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6% |
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 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%) Sources: Page: p.797Fatigue (grade 3, 33.3%) |
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
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 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
Title | Date | PubMed |
---|---|---|
Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. | 1991 Aug |
|
Interventions for herpes simplex virus epithelial keratitis. | 2001 |
|
Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. | 2001 Apr |
|
Antiviral drugs: current state of the art. | 2001 Aug |
|
In vitro effects of antiviral agents on human keratocytes. | 2001 Jan |
|
Effects of topical unoprostone and latanoprost on acute and recurrent herpetic keratitis in the rabbit. | 2001 May |
|
Interventions for herpes simplex virus epithelial keratitis. | 2003 |
|
Management of acyclovir-resistant herpes simplex virus. | 2003 Apr |
|
In vitro activity of potential anti-poxvirus agents. | 2003 Jan |
|
Recurrence of keratitis after excimer laser keratectomy. | 2003 Jan |
|
The effect of roscovitine on herpetic keratitis. | 2003 Jun |
|
Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity. | 2003 Mar 24 |
|
[Trifluridine therapy in herpetic in keratitis]. | 2004 Apr-Jun |
|
Management of ophthalmic zoster mucous plaque keratopathy: report of three cases. | 2004 Feb |
|
An optimal dosing schedule for a novel combination antimetabolite, TAS-102, based on its intracellular metabolism and its incorporation into DNA. | 2004 Feb |
|
Ocular vaccinia following exposure to a smallpox vaccinee. | 2004 Mar |
|
New onset of herpes simplex virus epithelial keratitis after penetrating keratoplasty. | 2004 Mar |
|
The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase. | 2004 May 3 |
|
Ocular complications in the Department of Defense Smallpox Vaccination Program. | 2004 Nov |
|
Association between ocular herpes simplex virus and topical ocular hypotensive therapy. | 2004 Oct |
|
Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis. | 2005 Nov |
|
Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs. | 2006 Aug 1 |
|
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 |
|
Evidence-based treatment of herpes simplex virus keratitis: a systematic review. | 2007 Jul |
|
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
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
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175595
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NDF-RT |
N0000175459
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NDF-RT |
N0000175459
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WHO-VATC |
QS01AD02
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WHO-ATC |
L01BC59
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FDA ORPHAN DRUG |
564116
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NDF-RT |
N0000175466
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NDF-RT |
N0000175459
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WHO-ATC |
S01AD02
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NCI_THESAURUS |
C1557
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200-722-8
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RMW9V5RW38
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D014271
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10803
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C448389
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1686309
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6256
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75179
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DB00432
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TRIFLURIDINE
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75520
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DTXSID4046602
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8697
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C905
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8126
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70-00-8
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M11125
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100000076935
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SUB11291MIG
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RMW9V5RW38
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4146
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529182
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2743
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CHEMBL1129
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)