Tipiracil (TPI) is a potent and competitive inhibitor of thymidine phosphorylase (TPase) with an IC50 value of 35 nM for human placental TPase.1 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.2
1.Fukushima, M., Suzuki, N., Emura, T., et al.Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2'-deoxyribonucleosidesBiochem. Pharmacol.59(10)1227-1236(2000) 2.Trebst, A., Wietoska, H., Draber, W., et al.The inhibition of photosynthetic electron flow in chloroplasts by the dinitrophenylether of bromo-or iodo-nitrothymolZ. Naturforsch. C J. Biosci.33(11-12)919-927(1978)