were performed using the Promega P450-Glo assay platform. Microsomal preparations of cytochrome P450s from baculovirus-infected insect cells were used. In this assay, light is generated when a CYP450 enzyme acts on its substrate and a decrease thereof was indicative of inhibitory effects of the tested compound on the respective isoform. For monitoring mitochondrial toxicity caused by the test compounds in the 786-O cell line, uptake of MitoTracker Red (chloromethyl-X-rosamine) combined with high content imaging was used. Cells were maintained in Rosswell Park Memorial Institute (RPMI)-1640 medium containing 2 mM glutamine, FCS (10% v/v), streptomycin (100 µg/mL), and penicillin G (100 U/mL). The cytotoxicity assay against A549 cells was performed using the CellTiter-Glo assay from Promega. The number of viable cells present is directly proportional to the cellular ATP content, which is detected. The A549 cells were obtained from DSMZ (German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany) and grown in Dulbecco's modified Eagle medium (DMEM) with FCS (10% v/v), streptomycin (100 µg/mL) and penicillin G (100 U/mL). Interference compounds; PTR1: Pteridine reductase 1; SI: Selectivity index; TS: Thymidylate synthase