Pteridine reductase 1 (PTR1) (PTR1)

Pteridine reductase 1 (PTR1) is an essential enzyme in the folate and pteridine metabolism of Trypanosoma brucei, the protozoan parasite responsible for Human African Trypanosomiasis (HAT) [1, 3]. Unlike most organisms that rely solely on dihydrofolate reductase (DHFR) for folate reduction, trypanosomatids utilize PTR1 as a broad-spectrum reductase capable of reducing both pterins (e.g., biopterin) and folates [3, 4]. This dual functionality allows PTR1 to serve as a metabolic bypass when DHFR is inhibited, contributing to the parasite's resistance to traditional antifolate drugs like methotrexate [4, 6]. PTR1 is considered a high-priority therapeutic target because its genetic knockdown or chemical inhibition leads to the depletion of reduced folates and pteridines, resulting in severe morphological defects, impaired cytokinesis, and parasite death [1, 8]. Current drug discovery efforts focus on developing potent PTR1 inhibitors, often in combination with DHFR inhibitors, to achieve synergistic anti-trypanosomal effects and overcome resistance mechanisms [6, 9].

Other names

Pteridine reductaseNADPH-dependent pteridine reductaseTbPTR1PTR1

Inhibition of PTR1 prevents the synthesis of reduced folates and pteridines essential for parasite survival and virulence, and blocks the metabolic bypass of dihydrofolate reductase (DHFR) inhibition [3, 4, 6].