fig2

Figure 2. The potentiating effect of maximal non-toxic concentrations of various statins on the CHR2863 activity in U937/WT, U937/CHR2863^R0.2 and U937/CHR2863^R5 cells. The concentrations of simvastatin, lovastatin, pravastatin and fluvastatin were 2 µM, 2.5 µM, 100 µM and 0.5 µM, respectively, for U937/WT cells, and 2.5 µM, 5 µM, 200 µM and 1 µM, respectively, for U937/CHR2863^R0.2 and U937/CHR2863^R5 cells. CHR2863 dose response curves in combination with statins were generated over a CHR2863 concentration range of 0-1 μM for U937/WT cells, 0-5 μM for U937/CHR2863^R0.2 cells and 0-50 μM CHR2863 for U937/CHR2863^R5 cells, essentially as shown in Figure 1. Statin potentiating factor is defined as the ratio of IC₅₀ (50% growth inhibition) of cell culture without statins vs. IC₅₀ of cell cultures in the presence of statins. Cell growth inhibition was determined after 72 h of drug exposure. The results depicted are the mean ± SD of 3-4 independent experiments. CHR2863: (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester.