CS-2890

BAM 15 is able to increase O ₂ consumption across a broad dosing range without increasing ROS. BAM 15 and FCCP are structurally unrelated and it is observed that low doses of BAM 15 from 100 nM to 1 μM increase cellular O ₂ consumption rate (OCR) to a similar degree as FCCP, but higher concentrations from 1 μM to 50 μM reveal that BAM 15 is able to maintain uncoupled respiration at a high rate in a range of cell lines. BAM 15 is fully capable of increasing mitochondrial respiration in the presence of oligomycin and does so across a broader concentration range than FCCP in both myoblasts and hepatocytes. BAM 15 induces mitochondrial swelling, demonstrating that BAM 15 is a protonophore. BAM15-treated cells are more viable than FCCP-treated cells when administered across a broad dosing range up to 50 μM.

Compare to vehicle-treated mice, animals that receive BAM 15 are protected from kidney injury as indicated by lower plasma creatinine levels at 24 and 48 h post-ischemia, reduced tubular necrosis, less depletion of brush border villi, less obstruction of proximal tubules, and less immune cell infiltration.