Description
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 linesIn Vitro5MPN (0~30 µM; 24 hours; H460 cells) inhibits the expression of PFKFB4. 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. 5MPN (0 and 10 µM; 6, 12 and 24 hours; H460 cells) induces cells apoptosis. 5MPN (0 and 10 µM; 6, 12 and 24 hours; H460 cells) arrests cell cycle progression. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: H460 cells Concentration: 0~30 µΜ Incubation Time: 24 hours Result: Inhibited the expression of PFKFB4. Cell Proliferation AssayCell Line: H460 NSCLC cells Concentration: 0~50 µM Incubation Time: 0~72 hours Result: Resulted in a reduction in cell proliferation. Apoptosis AnalysisCell Line: H460 cells Concentration: 0 and 10 µΜ Incubation Time: 6, 12 and 24 hours Result: Induced cells apoptosis. Cell Cycle AnalysisCell Line: H460 cells Concentration: 0 and 10 µΜ Incubation Time: 6, 12 and 24 hours Result: Arrested cell cycle progression.In Vivo5MPN (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. 5MPN causes a reduction in Ki67-positive cells in the LLC xenografts suggesting that 5MPN may be reducing cell cycle progression in vivo. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: C57BL/6 mice Dosage: 120 mg/kg Administration: P.o. Result: Suppressed 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.IC50& Target:KI: 8.6 µM (PFKFB4)