6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a bifunctional enzyme that contains distinct domains for the phosphorylation of fructose 6-phosphate and the dephosphorylation of fructose 2,6-bisphosphate. PFKFB3 protein expression is elevated in most tumor types. PFK15 is a selective inhibitor of PFKFB3 (IC50 = 207 nM). It has no significant inhibitory effect on any member of a panel of 96 other kinases, and does not inhibit purified 6-phosphofructo-1-kinase, hexokinase, phosphoglucose isomerase, or PFKFB4. PFK15 rapidly induces apoptosis in transformed cells, suppresses glucose uptake and growth of Lewis lung carcinomas in syngeneic mice, and yields antitumor effects in human xenograft models of cancer in athymic mice.
