Activators of PKM2 in cancer metabolism.

Pyruvate kinase converts phosphoenolpyruvate to pyruvate, catalyzing the rate-limiting step of glycolysis. The M1 isoenzyme of pyruvate kinase (PKM1) is found in adult tissues; whereas, PKM2 is a splicesome variant found in embryonic and cancer cells. PKM2 expression in malignant cells is a result of the tumor microenvironment and is responsible for maintaining a glycolytic phenotype.

A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas.

The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM) kinases (PIM-1, PIM-2, and PIM-3) are serine/threonine kinases that are involved in a number of signaling pathways important to cancer cells. PIM kinases act in downstream effector functions as inhibitors of apoptosis and as positive regulators of G1-S phase progression through the cell cycle. PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers.