Home DNA Damage/DNA Repair Thymidylate Synthase inhibitor - DNA/RNA Synthesis inhibitor TAS-102 For research use only.

TAS-102

Synonyms: Trifluridine-Tipiracil Hydrochloride Mixture

TAS-102 (Trifluridine-Tipiracil Hydrochloride Mixture) is an orally administered combination of a thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride.

TAS-102 Chemical Structure

TAS-102 Chemical Structure

CAS: 733030-01-8

Selleck's TAS-102 has been cited by 2 publications

Purity & Quality Control

Batch: Purity: 99.99%
99.99

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Biological Activity

Description TAS-102 (Trifluridine-Tipiracil Hydrochloride Mixture) is an orally administered combination of a thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride.
In vitro
In vitro

TAS-102 is an oral combination drug consisting of trifluridine (FTD), which is a thymidine-based nucleoside analog, and tipiracil hydrochloride (TPI), which improves the bioavailability of FTD by inhibiting its catabolism by thymidine phosphorylase (TP)[1].

Phosphorylated form of trifluridine is incorporated into DNA resulting in DNA dysfunction and cell cycle arrest. Thymidine phosphorylase inhibitor inhibits degradation of FTD and inhibits angiogenesis. Thus, TAS-102 treatment results in massive trifluridine incorporation into DNA and in activation of similar DNA damage response pathways, which involve phosphorylation of Chk1 and cycle arrest during the G2/M-phase[2].
Cell Research Cell lines Caco-2 cells
Concentrations 92.7 nM
Incubation Time 120 h
Method

Cells were treated with different concentrations of TAS-120.
In Vivo
In vivo

The elimination half-life of FTD after intravenous administration to humans is very rapid (18 minutes), due to the rapid degradation of FTD to its major metabolite, 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione. In monkeys, the plasma FTD level after oral administration alone is very low, suggesting extensive first-pass metabolism by the liver and intestine TPase. However, the addition of TPI(tipiracil hydrochloride) is found to enable oral administration. By inhibiting TP, TPI inhibits the degradation of FTD in the liver and intestines following oral administration and thereby improves its bioavailability. The TP enzyme catalyzes the phosphorolysis of pyrimidine 2'-deoxynucleosides such as FTD. Studies using human CRC tumor xenografts in mice determine that the maximum antitumor activity is achieved with a 1:0.5 molar ratio, and studies in mice and monkeys show that the maximum plasma concentration of FTD is almost achieved with the same ratio. Moreover, this ratio produces a favorable balance between antitumor activity and toxicity. Lower toxicity in mice is observed with TPI coadministration than with FTD alone. TAS-102 (FTD) can overcome acquired resistance to 5-FU because the main mechanism of TAS-102 is not associated with main metabolic enzymes of 5-FU, such as TS and OPRT. TAS-102 has demonstrated efficacy in 5-FU-refractory cancers[1].
Animal Research Animal Models Male nude mice
Dosages 150 mg/kg/day
Administration oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06039202 Not yet recruiting Metastatic Colorectal Cancer Holy Stone Healthcare Co. Ltd January 2024 Phase 2
NCT05343013 Recruiting Colorectal Cancer M.D. Anderson Cancer Center|Taiho June 6 2022 Phase 2
NCT04868773 Active not recruiting Colorectal Cancer|Colorectal Carcinoma|Metastatic Cancer|CRC University of California Irvine July 16 2021 Phase 1
NCT04074343 Active not recruiting Gastric Adenocarcinoma|GastroEsophageal Cancer University of California Irvine|Taiho Pharmaceutical Co. Ltd. August 26 2019 Phase 1

Chemical lnformation & Solubility

Molecular Weight 435.76 Formula

C10H11F3N2O5.0.5C9H11ClN4O2.0.5HCl
CAS No. 733030-01-8 SDF Download TAS-102 SDF
Smiles Cl.OCC1OC(CC1O)N2C=C(C(=O)NC2=O)C(F)(F)F.OCC3OC(CC3O)N4C=C(C(=O)NC4=O)C(F)(F)F.ClC5=C(CN6CCCC6=N)NC(=O)NC5=O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 87 mg/mL ( (199.65 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 44 mg/mL

Ethanol : Insoluble


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In vivo
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