piritrexim

Piritrexim is a synthetic, lipid-soluble antifolate and small molecule inhibitor of dihydrofolate reductase (DHFR), an enzyme essential for folate metabolism and DNA synthesis. By inhibiting DHFR, piritrexim disrupts the production of tetrahydrofolate, leading to impaired nucleotide synthesis and suppression of cell proliferation. Unlike classical antifolates such as methotrexate, piritrexim passively diffuses into cells and is not subject to polyglutamation or selective cellular retention. It has demonstrated antitumor, antipsoriatic, and antiparasitic properties in preclinical studies and clinical trials. Piritrexim has been investigated primarily for the treatment of bladder cancer, urethral cancer, transitional cell carcinoma of the renal pelvis/ureter, metastatic urothelial cancer, head and neck cancers (including methotrexate-resistant tumors), melanoma, gliomas/high-grade glioma, soft-tissue sarcomas, non-small cell lung cancers, breast cancer, mycosis fungoides (cutaneous T-cell lymphoma), and severe psoriasis[1][2][3][4][5][6][7]. The drug exhibits high oral bioavailability (~75%) with a short half-life (1.5–4.5 hours) due to hepatic metabolism[4][5]. Myelosuppression is the major dose-limiting toxicity; mucositis may also occur[7]. Piritrexim remains investigational with no current marketing approval.

Other names

piritreximapiritrexime72732-56-0