Thymidine phosphorylase (TP) (TP)

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is a cytosolic enzyme that plays a dual role in pyrimidine metabolism and angiogenesis [UniProt: P19971]. It catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxy-D-ribose-1-phosphate, a process essential for the nucleoside salvage pathway [NCBI: Gene ID 1890]. In the context of oncology, TP is frequently overexpressed in various solid tumors, where its enzymatic activity generates 2-deoxy-D-ribose, a sugar that stimulates endothelial cell migration and promotes tumor neovascularization [PubMed: 10491288]. Furthermore, TP is a critical pharmacological target because it mediates the intratumoral activation of fluoropyrimidine prodrugs such as capecitabine into 5-fluorouracil [DrugBank: DB00544]. Conversely, TP inhibitors like tipiracil are used to prevent the degradation of active nucleoside analogs like trifluridine, thereby maintaining therapeutic plasma levels [FDA: Lonsurf]. Deficiency of this enzyme due to genetic mutations leads to Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE), characterized by systemic accumulation of thymidine and deoxyuridine, leading to mitochondrial DNA instability [NCBI: NBK1179]. The provided name "DNA and thymidine phosphorylase" incorrectly combines two distinct therapeutic targets: the enzyme TP and the macromolecule DNA, which is the downstream site of action for many TP-regulated drugs.

Other names

Platelet-derived endothelial cell growth factorPD-ECGFGliostatinTYMPEC 2.4.2.4Thymidine:phosphate deoxyribosyltransferase

Thymidine phosphorylase (TP) acts as a metabolic activator for prodrugs (e.g., converting capecitabine to 5-FU) and as a target for inhibition (e.g., by tipiracil) to prevent the catabolism of active nucleoside analogs like trifluridine [DrugBank, FDA].