Definition

An orally bioavailable activator of pyruvate kinase M2 isoform (PKM2), with potential immunomodulating and antineoplastic activities. Upon oral administration, PKM2 activator TP-1454 locks PKM2 into the active tetrameric form. This may prevent the production of glycolytic intermediates by the less active dimer form of PKM2, depleting the supply of glycolytic intermediates which are needed for tumor cell growth. This may also inhibit immune suppression mediated by the dimer form of PKM2. Altogether, this may slow tumor cell growth and enhance anti-tumor immune responses, thereby inhibiting tumor cell proliferation. PKM2, the predominant PK isoform found in tumor cells, is responsible for catalyzing the last step of glycolysis. PKM2 plays a critical role in the metabolic changes observed in cancer and immune cells and establishes a metabolic advantage for tumor cells over the tumor immune microenvironment.