Dibenzylxanthines as PPEPCK-M inhibitors for cancer therapy

Phosphoenolpyruvate carboxykinase (PEPCK) is the key enzyme in gluconeogenesis/glyceroneogenesis, which catalyzes the decarboxylation of oxaloacetate to phosphoenolpyruvate. In eukaryotes, there are two isozymes present either in the cytosol (PEPCKC, PCK1) or the mitochondria (PEPCK-M, PCK2). While PCK1 is found in gluconeogenic tissues and has a very clear metabolic function, PCK2 is expressed in non-gluconeogenic cell types, where its role remains largely unknown. For example, PCK2 is highly expressed in most cancer cells, where it provides a growth advantage to cancer cells in nutrient-poor environments.