Drug Concentration kc(µM O2 min-1 mg-1) Inhibition (%) P Heart GSK2126458 0 0.48 ± 0.09 (6) - - 10 µM 0.39 ± 0.12 (11) 19 0.078 BEZ235 0 0.33 ± 0.08 (8) - - 0.1 µM 0.26 ± 0.07 (6) 21 0.142 10 µM 0.24 ± 0.12 (7) 27 0.040 GDC0980 0 0.37 ± 0.11 (8) - - 10 µM 0.29 ± 0.08 (16) 22 0.038 Liver GSK2126458 0 0.93 ± 0.20 (6) - - 10 µM 0.73 ± 0.18 (11) 22 0.048 BEZ235 0 0.87 ± 0.16 (4) - - 0.1 µM 0.60 ± 0.12 (8) 20 0.028 GDC0980 0 1.06 ± 0.24 (4) - - 0.1 µM 0.72 ± 0.16 (8) 32 0.016

Table 2: Effects of the PI3K/mTOR inhibitors on heart and liver cellular respiration. For each measurement, a tissue fragment was collected from C57BL/6 mouse and processed immediately for measuring cellular respiration in RPMI with and without designated concentrations of the drugs. The values of k c are mean ± SD (n); n=number of animals. Each measurement is a separate experiment.