BAY 87-2243

BAY 87-2243 is an inhibitor of mitochondrial complex I, also known as NADH:ubiquinone oxidoreductase, and an inducer of ferroptosis.^1,2 It decreases ATP-dependent luciferase reporter activity and ATP levels in H1299luc cells, effects that can be reversed by addition of the mitochondrial complex II substrate succinate or expression of the S. cerevisiae complex I ortholog Ndi1 NADH dehydrogenase.¹ BAY 87-2243 induces production of reactive oxygen species (ROS), increases α-tocopherol-sensitive lipid peroxidation, and decreases glutathione (GSH) levels in SK-MEL-28 and G361 melanoma cells, effects that can be partially reversed by the ferroptosis inhibitor ferrostatin-1 (Item No. 17729) and overexpression of GPX4 or potentiated by GPX4 knockdown.² In vivo, BAY 87-2243 (0.5-4 mg/kg) reduces tumor weight, hypoxia-inducible factor-1α (HIF-1α) levels, and HIF-1α target gene expression in an H460 mouse xenograft model.¹ It also reduces tumor growth in the MEXF 276 and MEXF 1732 melanoma patient-derived xenograft (PDX) mouse models.³

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1. Ellinghaus, P., Heisler, I., Unterschemmann, K., et al. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2(5), 611-624 (2013).

2. Basit, F., van Oppen, L.M., Schöckel, L., et al. Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis. 8(3), e2716 (2017).

3. Schöckel, L., Glasauer, A., Basit, F., et al. Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth. Cancer Metab. 3:11, (2015).