Pralatrexate

An antifolate that fuctions as a dihydrofolate reductase inhibitor for treatment of several malignancies.Chemotherapeutic Agents Approved (In Vitro) :Pralatrexate (100 pM-200 μM; 48-72 hours; T-lymphoma cell lines) treatment exhibits concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. The IC50 values at 48 and 72 hours, respectively, are as follows: H9 cells, 1.1 nM and 2.5 nM; P12 cells, 1.7 nM and 2.4 nM; CEM cells, 3.2 nM and 4.2 nM; PF-382 cells, 5.5 nM and 2.7 nM; KOPT-K1 cells, 1 nM and 1.7 nM; DND-41 cells, 97.4 nM and 1.2 nM; and HPB-ALL cells, 247.8 nM and 0.77 nM. HH cells are relatively resistant after 48 hours of exposure, with the IC50 at 72 hours being 2.8 nM.Pralatrexate (2-5.5 nM; 48-72 hours; H9, HH, P12 and PF382 cells) treatment induces potent apoptosis, and caspase-8 and caspase-9 activation.Pralatrexate (3 nM; 16-48 hours; H9 and P12 cells) treatment clearly increases p27 levels and increases the accumulation of educed folate carrier type 1 (RFC-1) in cells. (In Vivo) :The addition of Pralatrexate (15 mg/kg; intraperitoneal injection; on days 1, 4, 8, and 11; SCID-beige mice) to Bortezomib (0.5 mg/kg) enhanced efficacy compared with either drug alone.