talotrexin

Talotrexin (PT523) is a potent, non-polyglutamatable antifolate small molecule that acts as a competitive inhibitor of dihydrofolate reductase (DHFR). By inhibiting DHFR, talotrexin depletes intracellular reduced folate pools, thereby inhibiting the synthesis of thymidylate and purines, which are essential for DNA replication and cell division. Unlike methotrexate, talotrexin does not require polyglutamylation for its inhibitory activity, which potentially allows it to bypass resistance mechanisms associated with defective polyglutamylation or reduced folate carrier transport. It was investigated in Phase I and II clinical trials for various malignancies, including solid tumors, non-small cell lung cancer (NSCLC), and acute lymphoblastic leukemia (ALL). Development was primarily driven by Hana Biosciences (later Talon Therapeutics) in collaboration with institutions like the Dana-Farber Cancer Institute.

Brand names

Talvesta

Other names

talotrexin ammonium