Recent advances in the synthetic thymidine phosphorylase inhibitors for cancer therapy

Thymidine phosphorylase (TP) is an important enzyme for the synthesis and decomposition of pyrimidine, which can specifically catalyze the reversible phosphorolysis of thymidine to thymine and 2-deoxy-alpha-D-ribose-1-phosphate in the body. TP is highly expressed in many solid tumor tissues and can induce angiogenesis and anti-apoptotic effect, as well as tumor growth and metastasis. Therefore, TP inhibitors play a major role in the treatment. In recent years, a large number of synthetic TP inhibitors have been widely reported. In this article, the research progress of synthetic TP inhibitors was reviewed, including inhibitory activity, cytotoxicity, structure-activity relationship (SAR), inhibitory kinetics, mechanism of interaction and molecular docking. In our reviewed inhibitors, pyrimidine derivatives account for about a half, but it is a lack for research on other bio-logical activities of pyrimidine derivatives and further exploration of the inhibitory mechanism of excellent inhibitors. Meanwhile, application of radiolabeled inhibitors to assess TP expression in tumors and prognosis of cancer chemotherapy in vivo is rarely reported. In addition, the study on the synergistic anticancer activity of TP inhibitors in combination with other anticancer drugs is less. Therefore, it is valuable to look forward to developing more and more potent TP inhibitors and applying them in the clinical treatment of cancer in the future.

Automated summary

Thymidine phosphorylase (TP) is an important enzyme involved in the synthesis and decomposition of pyrimidine. TP inhibitors have shown significant potential in cancer treatment due to their ability to inhibit angiogenesis, induce anti-apoptotic effects, and inhibit tumor growth and metastasis. In this article, the research progress of synthetic TP inhibitors was reviewed. However, there is a lack of research on the biological activities and inhibitory mechanisms of pyrimidine derivatives, as well as the application of radiolabeled inhibitors in assessing TP expression and the synergistic anticancer activity of TP inhibitors in combination with other drugs.