Trifluridine and Tipiracil Hydrochloride

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable combination agent composed of the cytotoxic pyrimidine analog trifluridine (5-trifluoro-2'-deoxythymidine or TFT) and a thymidine phosphorylase inhibitor (TPI) tipiracil hydrochloride, in a molar ratio of 1.0:0.5 (TFT:TPI), with potential antineoplastic activity. After oral administration of TAS-102, TFT is phosphorylated to the active monophosphate form TF-TMP, which binds covalently to the active site of thymidylate synthase, thereby reducing the nucleotide pool levels required for DNA replication. Furthermore, the triphosphate form TF-TTP can be incorporated into DNA, which induces DNA fragmentation and leads to the inhibition of tumor growth. TPI exhibits a dual effect: 1) an anti-angiogenic effect mediated through the inhibition of thymidine phosphorylase, which plays important role in nucleotide metabolism and a variety of development processes, including angiogenesis, 2) increased bioavailability of the normally short-lived antimetabolite TFT by preventing its degradation into the inactive form trifluorothymine (TF-Thy). The synergistic effect of the components in TAS-10 may demonstrate antitumor activity in 5-FU-resistant cancer cells.

**Synonyms:** - FTD-TPI - Lonsurf - TAS 102 - TAS-102 - TAS102 - Thymidine, Alpha,alpha,alpha-trifluoro-, Mixt. with 5-Chloro-6-((2-imino-1-pyrrolidinyl)methyl)-2,4(1H,3H)-pyrimidinedione Monohydrochloride - Tipiracil Hydrochloride Mixture with Trifluridine - Trifluridine and Tipiracil - Trifluridine and tipiracil - Trifluridine/Tipiracil - Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102