Tipiracil hydrochloride Chemical Properties

Melting point:

245℃ (decomposition)

storage temp. 

2-8°C

solubility 

DMSO (Slightly, Heated), Water (Slightly)

form 

powder

color 

white to beige

Water Solubility 

H2O: 5mg/mL, clear (warmed)

Stability:

Hygroscopic

InChI

InChI=1S/C9H11ClN4O2.ClH/c10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11;/h11H,1-4H2,(H2,12,13,15,16);1H

InChIKey

KGHYQYACJRXCAT-UHFFFAOYSA-N

SMILES

C1(=O)NC(CN2CCCC2=N)=C(Cl)C(=O)N1.[H]Cl

Tipiracil hydrochloride Usage And Synthesis

Description

Tipiracil (TPI) is a potent and competitive inhibitor of thymidine phosphorylase (TPase) with an IC₅₀ value of 35 nM for human placental TPase. It is selective for TPase over other pyrimidine-metabolizing enzymes (IC₅₀s = >1 mM for UPase, OPRTase, TK, and DPDase). TPI inhibits the phosphorolysis and degradation of trifluorothymidine , a cytotoxic nucleoside, in human breast and colon carcinoma tumor samples. Oral administration of TPI (12.5-50 mg/kg) enhances the anti-tumor activity of trifluorothymidine in a mouse AZ-521 stomach cancer xenograft model. Formulations containing TPI have been used for the treatment of metastatic colorectal cancer.

Uses

Tipiracil Hydrochloride serves as a treatment for metastatic colorectal cancer (mCRC). A thymidine phosphorylase inhibitor.

Definition

ChEBI: Tipiracil hydrochloride is a hydrochloride obtained by combining tipiracil with one equivalent of hydrochloric acid. Used in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer. It has a role as an antineoplastic agent and an EC 2.4.2.4 (thymidine phosphorylase) inhibitor. It is a hydrochloride and an iminium salt. It contains a tipiracil(1+).

Biochem/physiol Actions

Tipiracil is an inhibitor of thymidine phosphorylase. Tipiracil is used in combination with trifluridine as TAS-102 for the treatment of refractory metastatic colorectal cancer. Tipiracil increases the bioavailability of trifluridine by blocking the enzyme that would otherwise protect the tumors by metabolizing trifluridine.

target

thymidine phosphorylase

References

[1] MASAKAZU FUKUSHIMA . Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2′-deoxyribonucleosides[J]. Biochemical pharmacology, 2000, 59 10: Pages 1227-1236. DOI:10.1016/S0006-2952(00)00253-7.
[2] Kim, Y., Wower, J., Maltseva, N.I., et al. Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2. Commun. Biol. 4(1), 193 (2021).
[3] HIROSHI TSUKIHARA. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts.[J]. Oncology reports, 2015, 33 5: 2135-2142. DOI:10.3892/or.2015.3876.
[4] D L DEXTER. The clinical pharmacology of 5-trifluoromethyl-2’-deoxyuridine.[J]. Cancer research, 1972, 32 2: 247-253.

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