Small-molecule inhibitors of 6-phosphofructo-1-kinase simultaneously suppress lactate and superoxide generation in cancer cells
Fig 3
Half maximal inhibitory concentrations (IC50) of selected compounds.
In the graphs, the red horizontal lines present the intersections among the concentrations of modified sfPFK-M enzymes, while horizontal blue lines are from native nPFK-M enzymes. The vertically dashed line shows the half-maximal PFK-M activities of enzymes treated by different concentrations of selected compounds. Selected compounds were evaluated for their ability to reduce purified human PFK1 enzyme activities in vitro. Cmpds No. 3 and 9, which preferentially bind to the ATP-binding site of PFK-M, inhibited both the native (85 kDa) enzyme and the shorter (47 kDa) fragment. Still, more significant inhibition was observed in modified, cancer-specific shorter forms. Reaching IC50 relative activity at cmpd No. 3, 15 µM and cmpd No. 9, 17 µM). In contrast, more significant differences were observed between the inhibitions of native and modified PFK-L enzymes. At lower concentrations, almost no deactivation of the native (85 kDa) activity was observed. However, more effective inhibition of the shorter (70 kDa) fragment of modified PFK-L was observed with cmpd No. 29, 30 (IC50 8 µM) and cmpd No. 31, 32 (IC50 9 µM). The data represents three independent measurements and are given as mean ±(SD) mean (n = 3).