3PO is an inhibitor of the metabolic enzyme 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3). PFKFB3 is constitutively expressed by neoplastic cells and is required for the high glycolytic rate (Warburg Effect) of these cells. 3PO inhibits PFKFB3 (IC50 = 1.4 - 24 µM for various cancer cell lines), suppresses glucose uptake, and lowers intracellular concentrations of Fru-2,6-BP, lactate, ATP, NAD+, and NADH.1 Inhibition of cancer cell metabolism via blocking the action of PFKFB3 has been studied in various models.2-4 Inhibition of PFKFB3 has been shown to induce autophagy as a survival mechanism in cancer cells.5 3PO has also been used to reduce pathological angiogenesis.6
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