5MPN

5MPN is a first-in-class, potent, orally active and selective 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) inhibitor. 5MPN appears to be a competitive inhibitor of the F6P binding site (K_i=8.6 μM). 5MPN does not inhibit PFK-1 or PFKFB3. 5MPN targets the sugar metabolism of tumors and suppresses proliferation of multiple human cancer cell lines^[1]. IC50 & Target: KI: 8.6 μM (PFKFB4)^[1] In Vitro: 5MPN (0~30 μM; 24 hours; H460 cells) inhibits the expression of PFKFB4^[1].
5MPN (0~50 μM; 0~72 hours; H460 NSCLC cells) first reduces the intracellular concentration of F2,6BP, glycolysis and ATP, which in turn results in a reduction in cell proliferation^[1].
5MPN (0 and 10 μM; 6, 12 and 24 hours; H460 cells) induces cells apoptosis^[1].
5MPN (0 and 10 μM; 6, 12 and 24 hours; H460 cells) arrests cell cycle progression^[1].
5MPN (0.1, 1 or 10 µM) significantly inhibits PFKFB4 activity. 5MPN (H460 cells) leads to a dose-dependent decrease in the intracellular F2,6BP concentration. 5MPN (0~30 μM; over 48 hours; H460, H1299, H441, H522 and A549 cells) makes a dose-dependent reduction in cells growth. 5MPN (0~30 μM; 24 hours; H460 cells) inhibits PFKFB4 expression causing the observed reduction in H460 cell proliferation. 5MPN causes a G1 arrest in LLC cells in vitro similar to H460 cells^[1]. In Vivo: 5MPN (120 mg/kg; p.o.) suppresses the growth of Lewis lung carcinomas (LLC) grown in syngeneic mice and H460 human lung adenocarcinoma xenografts grown in athymic mice without affecting body weight^[1].
5MPN causes a reduction in Ki67-positive cells in the LLC xenografts suggesting that 5MPN may be reducing cell cycle progression in vivo^[1].