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外観
白色～ほとんど白色粉末～結晶
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効能
抗ウイルス薬, 核酸合成阻害薬
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説明
Trifluridine (trifluorothymidine, TFT), a fluorinated pyrimidine nucleoside, is an anti-herpesvirus agent and an antitumor antimetabolite agent. It is an analog of thymidine which inhibits thymidylate synthase possesses antiviral and anticancer activity. After phosphorylation by thymidine kinase, it is incorporated into DNA where it induces DNA-damage and interferes with repair enzymes. Enhances frame shift insertion and deletion in CRISPR genome editing in pluripotent stem cells.
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化学的特性
White to Off-White Solid
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使用
Trifluridine is used as anti-herpesvirus antiviral agent in ophthalmie preparations.
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適応症
Trifluridine (Viroptic) is a fluorinated pyrimidine nucleoside
that has in vitro activity against HSV-1 and HSV-
2, vaccinia, and to a lesser extent, some adenoviruses.
Activation of trifluridine requires its conversion to the
5 monophosphate form by cellular enzymes.Trifluridine
monophosphate inhibits the conversion of deoxyuridine
monophosphate (dUMP) to deoxythymidine
monophosphate (dTMP) by thymidylate synthetase. In
addition, it competes with deoxythymidine triphosphate
(dTTP) for incorporation by both viral and cellular
DNA polymerases. Trifluridine-resistant mutants have
been found to have alterations in thymidylate synthetase
specificity.
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定義
ChEBI: Trifluridine is a pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis. It has a role as an antiviral drug, an antimetabolite, an EC 2.1.1.45 (thymidylate synthase) inhibitor and an antineoplastic agent. It is a nucleoside analogue, an organofluorine compound and a pyrimidine 2'-deoxyribonucleoside.
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一般的な説明
Trifluridine, 5-trifluoromethyl-29-deoxyuridine (Viroptic),is a fluorinated pyrimidine nucleoside that demonstrates invitro inhibitory activity against HSV-1 and HSV-2, CMV,vaccinia, and some adenoviruses.Trifluridine possesses atrifluoromethyl group instead of an iodine atom at the 5-position of the pyrimidine ring.
synthetase, and the biologically generated triphosphatecompetitively inhibits thymidine triphosphate incorporationinto DNA by DNA polymerase. In addition, trifluridine inits triphosphate form is incorporated into viral and cellularDNA, creating fragile, poorly functioning DNA.Trifluridine is approved in the United States for the treatmentof primary keratoconjunctivitis and recurrent epithelialkeratitis caused by HSV types 1 and 2. Topical trifluridineshows some efficacy in patients with acyclovir-resistantHSV cutaneous infections.
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作用機序
Trifluorothymidine is a fluorinated pyridine nucleoside structurally related to idoxuridine. It has been
approved by the U.S. FDA and is a potent, specific inhibitor of replication of HSV-1 in vitro. Its
mechanism of action is similar to that of idoxuridine. Like other antiherpes drugs, it is first
phos-phorylated by thymidine kinase to mono-, di-, and triphosphate forms, which are then incorporated
into viral DNA in place of thymidine to stop the formation of late virus mRNA and subsequent synthesis of
the virion proteins.
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薬物動態学
Trifluorothymidine is a synthetic halogenated pyrimidine nucleoside, first synthesized as an antitumor agent. It inhibits enzymes of the DNA pathway and is incorporated into both cellular and progeny viral DNA, causing faulty transcription of late messenger RNA and the production of incompetent virion protein. It does not require a viral thymidine kinase for monophosphorylation and is far less selective and more toxic than other analogs. It is active against HSV-1 and HSV-2, vaccinia virus, CMV and possibly adenovirus. Trifluorothymidine, when given IV, shows a plasma half-life of 18 minutes and is excreted in the urine either unchanged or as the inactive metabolite 5-carboxyuracil. When applied as a 1% ophthalmic solution, it rapidly enters the aqueous humor of HSV-infected rabbits’ eyes but is cleared within 60–90 min.
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副作用
The most frequent adverse reactions to trifluridine administration
are transient burning or stinging and
palpebral edema. Other adverse reactions include superficial
punctate keratopathy, epithelial keratopathy,
hypersensitivity, stromal edema, irritation, keratitis
sicca, hyperemia, and increased intraocular pressure.
Trifluridine is mutagenic in vitro and carcinogenic
and teratogenic when administered subcutaneously to
animals. Topical trifluridine was not teratogenic in animal
studies. Because it is applied topically in humans,
the likelihood of systemic effects is low.
