Background:

3PO is a novel small-molecule inhibitor of the PFKFB3 isozyme, 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 μM) IC50 valueTarget: PFKFB3 isozymein vitro: 3PO inhibits recombinant PFKFB3 activity, suppresses glucose uptake, and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+, and NADH. 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 μM) and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronchial epithelial cells. The PFKFB3+/- fibroblasts were more sensitive to compound 3PO treatment (IC50, 26 μM) compared with the wild-type PFKFB3+/+transformed cells (IC50, 49 μM).3PO Causes G2-M Phase Arrest, Which Is Preceded by Decreased Fru-2,6-BP and Glucose Uptake. 3PO slows growth through inhibition of PFK-2 activity, then ectopic expression of the PFKFB3 isozyme may thwart the cytostatic activity of 3PO. [1] 3PO inhibits the glycolytic regulator PFKFB3 in endothelial cells (ECs). 3PO decreases glycolysis in ECs and impairs vessel sprouting. 3PO also suppresses vascular hyperbranching induced by inhibition of Notch or VEGF receptor 1 (VEGFR1) and amplified the antiangiogenic effect of VEGF blockade. [2]in vivo: Compound 3PO treatment significantly reduced Fru-2,6-BP in tumor xenografts compared with vehicle control (vehicle: 13.1 ± 1.9 pmol/mg, 3PO: 8.5 ± 1.7 pmol/mg). [1] 3PO also impairs (pathological) angiogenesis. [2]

参考文献:
[1]. Clem B, et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol Cancer Ther. 2008 Jan;7(1):110-20.
[2]. Schoors S, et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab. 2014 Jan 7;19(1):37-48.
[3]. Lea MA, Inhibition of Growth of Bladder Cancer Cells by 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one in Combination with Other Compounds Affecting Glucose Metabolism. Anticancer Res. 2015 Nov;35(11):5889-99.