Pralatrexate (PDX or 10-propargyl-10-deazaaminopterin) is a folate analogue that is internalised by the reduced folate carrier 1 (RFC-1) protein, and polyglutamylated by the enzyme folylpolyglutamyl synthetase (FPGS), resulting in accumulation of the antifolate. Pralatrexate, a methotrexate analogue, is intended as an inhibitor of dihydrofolate reductase (DHFR), an enzyme which catalyses the reduction of dihydrofolic acid to tetrahydrofolic acid. Inhibition of DHFR leads to a depletion of intracellular reduced folate stores, thereby leading to a disruption of DNA synthesis. Preclinical studies in vitro and in models of B-cell lymphomas, T-cell lymphomas and NSCLC indicated that pralatrexate exhibited antitumor activity that was superior to the activity of other antifolates. FOLOTYN (pralatrexate injection) is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. NCATS
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