trifluridine   Click here for help

GtoPdb Ligand ID: 8697

Synonyms: TFT | trifluorothymidine
Approved drug
trifluridine is an approved drug (Japan, FDA (2015), EMA (2016))
Compound class: Synthetic organic
Comment: 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.

trifluridine is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 104.55
Molecular weight 296.06
XLogP 0.1
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES OCC1OC(CC1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F
Isomeric SMILES OC[C@H]1O[C@H](C[C@@H]1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F
InChI 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
InChI Key VSQQQLOSPVPRAZ-RRKCRQDMSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Trifluridine is a component of the anticancer therapeutic Lonsurf® (code-named TAS-102), that was first approved in Japan for the treatment of metastatic/unresectable colorectal cancer. The other component of TAS-102 is tipiracil [1]. In September 2015, the US FDA approved Lonsurf® for the treatment of patients with RAS wild type, metastatic colorectal cancer who have already received chemotherapy, anti-VEGF, and anti-EGFR therapies. Lonsurf® was EMA approved in 2016. TAS-102 is being assessed in Phase 3 clinical trial for metastatic gastric cancer (NCT02500043).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Trifluridine is a modified form of deoxyuridine (nucleoside analogue). Trifluridine is metabolised to its monophosphate-derivative and this inhibits thymidylate synthase, one of the rate-limiting enzymes in pyrimidine de novo deoxynucleotide synthesis. Thymidylate synthase is therefore crucial for DNA synthesis. In addition, if trifluridine is incorporated directly in to DNA during replication, the -CF3 group of trifluridine blocks base pairing. These actions underly the compound's cytotoxic effect [2].
External links Click here for help
For extended ADME data see the following:

Drugs.com