Trifluridine/tipiracil hydrochloride mixture

SKU: orb1303948

Description

Trifluridine/tipiracil hydrochloride mixture

Research Area

Cell Biology, Molecular Biology

Key Properties

• CAS Number: 733030-01-8
• MW: 871.53
• Purity: 99.82%
• Formula: C₂₉H₃₄Cl₂F₆N₈O₁₂
• SMILES: Cl.Clc1c(CN2CCCC2=N)[nH]c(=O)[nH]c1=O.OC[C@H]1O[C@H](C[C@@H]1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F.OC[C@H]1O[C@H](C[C@@H]1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F
• Target: DNA/RNA Synthesis,Nucleoside Antimetabolite/Analog
• Solubility: DMSO:100 mg/mL (114.74 mM);H2O:50 mg/mL (57.37 mM);Ethanol:100 mg/mL (114.74 mM)

Bioactivity

• 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 b the liver and intestine TPase. however the addition of TPI(tipiracil hydrochloride) is found to enable oral administration. By inhibiting TP, TPI inhibit the degradation of FTD in the liver and intestines following oral administration and thereby improves its bioavailability the TP enzyme catalyze the phosphorolysis of pyrimidine 2'-deoxynucleosides such as FTD. Studies using human CRC tumor xenografts in mice determine tha the maximum antitumor activity is achieved with a 1:0.5 molar ratio, and studies in mice and monkeys show tha the maximum plasma concentration of FTD is almost achieved wit 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. Trifluridine/tipiracil hydrochloride mixture (FTD) can overcome acquired resistance to 5-FU becaus the main mechanism of Trifluridine/tipiracil hydrochloride mixture is not associated with main metabolic enzymes of 5-FU, such as TS and OPRT. Trifluridine/tipiracil hydrochloride mixture has demonstrated efficacy in 5-FU-refractory cancer.
• In Vitro:
  Trifluridine/tipiracil hydrochloride mixture is an oral combination drug consisting of trifluridine (FTD), which is a thymidine-based nucleoside analog, and tipiracil hydrochloride (TPI), which improve the bioavailability of FTD by inhibiting its catabolism by thymidine phosphorylase (TP. 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, Trifluridine/tipiracil hydrochloride mixture 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 durin the G2/M-phas.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

DNASynthesis, DNA, DNA Synthesis, DNA/RNA Synthesis, Analog, antitumor, FTD, Inhibitor, NucleosideAntimetabolite, Nucleoside Antimetabolite/Analog, Nucleoside Antimetabolite, nucleoside, oral, inhibit, Thymidylate Synthase, RNA Synthesis, RNASynthesis, TAS 102, TAS102, TAS-102, TPI, Trifluridine/tipiracil hydrochloride mixture, Trifluridine-tipiracil hydrochloride mixture

Compound Identifiers

PubChem CID

10373441