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| Name | Trifluridine | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00432 (APRD01275) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||
| Description | An antiviral derivative of thymidine used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557) |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Brand names |
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| Brand mixtures | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 70-00-8 | ||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 296.1999 Monoisotopic: 296.062006087 |
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| Chemical Formula | C10H11F3N2O5 | ||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=VSQQQLOSPVPRAZ-RRKCRQDMSA-N | ||||||||||||||||||||||||||||||||||||||||||
| 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
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| IUPAC Name |
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione
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| SMILES |
OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||
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| Substructures |
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| Pharmacology | |||||||||||||||||||||||||||||||||||||||||||
| Indication | Ophthalmic solution for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. Some strains of adenovirus are also inhibited in vitro. Trifluridine 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, trifluridine was also effective. Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known. | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | 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. This drug also reversibly inhibits thymidylate synthetase, an enzyme that is necessary for DNA synthesis. | ||||||||||||||||||||||||||||||||||||||||||
| Absorption | Systemic absorption of trifluridine following therapeutic dosing with trifluridine ophthalmic appears to be negligible. | ||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Protein binding | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Metabolism | One major metabolite, 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea, indicating localized metabolism. | ||||||||||||||||||||||||||||||||||||||||||
| Route of elimination | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Half life | Approximately 12 to 18 minutes following ophthalmic administration. | ||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac. Acute overdosage by accidental oral ingestion has not occurred. However, should such ingestion occur, the 75 mg dosage of trifluridine in a 7.5 mL bottle of trifluridine is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD50 in the mouse and rat was 4379 mg/kg or higher. | ||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational
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| Patents | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Properties | |||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| General Reference |
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| FDA label | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| MSDS | show (55.2 KB) | ||||||||||||||||||||||||||||||||||||||||||
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| Drug Interactions | Searched, but no interactions found. | ||||||||||||||||||||||||||||||||||||||||||
| Food Interactions | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Targets |
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Pharmacological action: yes
Actions: inhibitor Organism class: human UniProt ID: P04818 ![]() Gene: TYMS ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. DNA Pharmacological action: yesActions: other/unknown DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes. Gene Sequence: FASTAReferences:
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| Enzymes |
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1. Thymidine kinase, cytosolic Actions: substrateATP + thymidine = ADP + thymidine 5'- phosphate UniProt ID: P04183![]() Gene: TK1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis UniProt ID: P19971![]() Gene: ECGF1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Transporters |
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1. Solute carrier family 22 member 6 Actions: inhibitorUniProt ID: Q4U2R8 ![]() Gene: hROAT1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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