General
Preferred name
trifluridine
Synonyms
5-Trifluorothymidine ()
Trifluorothymidine ()
NSC 529182 ()
NSC 75520 ()
Viroptic ()
Trifluridina ()
Trifluridine (NSC 75520) ()
NSC 529182, NSC 75520, Viroptic, Trifluorothymidine, TFT ()
Triherpine ()
T.F.T. ()
F3DThd ()
NSC-75520 ()
Trifluridine ()
NSC-529182 ()
Trifluridine ()
Trifluorothymidine ()
P&D ID
PD010030
CAS
70-00-8
Tags
natural product
drug
available
Approved by
PMDA
FDA
First approval
1980
Drug Status
investigational
approved
Drug indication
Virus infection
Antiviral (ophthalmic)
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Trifluridine exhibits an antiviral effect against herpes simplex virus, types 1 and 2 and vacciniavirus both in vitro and in vivo [A35271]. Some strains of adenovirus that contribute to the pathology of keratoconjunctivitis were shown to be susceptible to trifluridine _in vitro_ [A35271]. While there is evidence from a study that cross-resistance may develop between trifluridine and [idoxuridine] or [vidarabine], trifluridine was shown to effective in treating dendritic ulcers in patients with herpetic keratitis who are unresponsive to [idoxuridine] or [vidarabine] based on the results from masked comparative trials [A35271]. In nonclinical studies, trifluridine/tipiracil hydrochloride demonstrated antitumour activity against both 5-fluorouracil (5-FU) sensitive and resistant colorectal cancer cell lines [F649]. The cytotoxic activity of trifluridine and tipiracil against several human tumour xenografts show high correlation with the amount of trifluridine incorporated into DNA, indicating that the primary mechanism of action of trifluridine involves the direct incorporation into the cancer cell DNA [F649]. Trifluridine and tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in mice [FDA Label]. ; ; In clinical studies comprised of patients with previously treated metastatic colorectal cancer, treatment of trifluridine in combination with tipiracil in addition to best supportive care over a 5- or 7-month period resulted in increased progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) compared to placebo [F649]. In an open-label study, administration of trifluridine at the recommended dosage in patients with advanced solid tumors had no clinically relevant effect on QT/QTc prolongation compared with placebo [FDA Label]. Two out of 48 patients displayed had QTc greater than 500 msec and 1 of 42 patients (2.4%) had a QTc increase from baseline greater than 60 msec [FDA Label].
DESCRIPTION
Trifluridine was originally approved by the US FDA in 1980, and was used for its antiviral effects (marketed as Vitroptic®). The drug is now being investigated for its antineoplastic (cytotoxic) effect.
(GtoPdb)
HALF-LIFE
The half life is 12 to 18 minutes following ophthalmic administration [F658].; ; After administration of trifluridine with tipiracil at oral doses 35 mg/m^2 twice daily, the mean elimination half-life (t1/2) of trifluridine was 1.4 hours following a single dose [FDA Label]. At steady state, the mean elimination half-life was 2.1 hours [FDA Label].
ABSORPTION
Systemic absorption of trifluridine following therapeutic dosing with ophthalmic trifluridine appears to be negligible [F658]. ; ; At least 57% of the orally-administered trifluridine is absorbed [F649]. Following twice daily oral dosing of trifluridine in combination with tipiracil, systemic exposure of trifluridine increased more than dose-proportionally over the dose range of 15 to 35 mg/m^2. Trifluridine accumulation was 3-fold for AUC0-last and 2-fold for peak plasma concentration (Cmax) at steady state [FDA Label]. The time to reach the peak plasma concentrations (Cmax) was 2 hours [FDA Label]. Tipiracil increases the AUC and Cmax of trifluridine. Food intake was shown to decrease the Cmax and AUC compared to those in a fasting state [F649].
METABOLISM
One major metabolite, 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea, indicating localized metabolism [A35307, F658].; ; Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase (TPase) to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY) [FDA Label].
INDICATION
Trifluridine is used for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2 in ophthalmic solutions.; ; Trifluridine, in combination with tipiracil as oral tablets, is indicated for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy [FDA Label].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
3
Compound Sets
18
AdooQ Bioactive Compound Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
NCATS Inxight Approved Drugs
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
42
Molecular Weight
296.06
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
3
Rotatable Bonds
2
Ring Count
2
Aromatic Ring Count
1
cLogP
-0.8
TPSA
104.55
Fraction CSP3
0.6
Chiral centers
3.0
Largest ring
6.0
QED
0.66
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
DNA Damage/DNA Repair
Target
DNA/RNA Synthesis
Thymidylate Synthase
TYMS
DNA/RNA Synthesis,Thymidylate Synthase
MOA
DNA directed DNA polymerase inhibitor, thymidylate synthase inhibitor
Indication
virus herpes simplex (HSV)
Therapeutic Class
Antiviral Agents
Source data
