Drug Concentration kc (µM O2 min-1 mg-1) Inhibition (%) P GSK2126458 (PI3K/mTOR inhibitor) 0 1.12 ± 0.27 (22) - - 0.1 µM 1.36 ± 0.23 (4) 0 0.150 1.0 µM 1.02 ± 0.19 (9) 9 0.453 10 µM 0.74 ± 0.18 (11) 34 <0.001 BEZ235 (PI3K/mTOR inhibitor) 0 0.72 ± 0.18 (18) - - 0.1 µM 0.75 ± 0.20 (8) 0 0.724 1.0 µM 0.62 ± 0.15 (16) 16 0.126 10 µM 0.40 ± 0.13 (10) 31 <0.001 GDC0980 (PI3K/mTOR inhibitor) 0 0.93 ± 0.20 (12) - - 0.1 µM 0.98 ± 0.21 (7) 0 0.400 1.0 µM 0.62 ± 0.07 (8) 27 <0.001 10 µM 0.64 ± 0.10 (12) 26 0.003 GSK1120212 (MEK inhibitor) 0 1.30 ± 0.32 (4) - - 10 µM 1.03 ± 0.18 (7) 21 0.164 Cyclosporine (calcineurin inhibitor) 0 1.07 ± 0.17 (4) - - 10 µM 1.00 ± 0.23 (8) 7 0.461 Sorafenib (multikinase inhibitor) 0 0.96 ± 0.18 (6) - - 10 µM 0.90 ± 0.22 (12) 6 0.494 Regorafenib (multikinase inhibitor) 0 1.02 ± 0.28 (4) - - 10 µM 1.01 ± 0.20 (8) 0 1.00

Table 1: Effects of selected inhibitors of protein kinases and phosphatases on renal cellular respiration. For each measurement, a renal 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.