3PO is a competitive inhibitor of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase 3 (PFKFB3; IC50 = 23 μM) that causes a rapid reduction in fructose 2,6-bisphosphate (F2,6BP), glucose uptake, and lactate secretion. This is followed by a reduction in the steady-state concentration of ATP and NADH, resulting in cell cycle arrest in Jurkat T cell leukemia cells. 3PO is selectively cytostatic to ras-transformed bronchial epithelial cells relative to normal bronchial epithelial cells. 3PO markedly reduces intracellular F2,6BP, glucose uptake, and growth of established tumors in mice. It also blocks angiogenesis, reducing vessel sprouting in endothelial cell spheroids, zebrafish embryos, and the postnatal mouse retina by inhibiting endothelial cell proliferation and migration.
