BAY-87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. BAY 87-2243 inhibits HIF-1 reporter gene activity and CA9 protein expression with IC50 of 0.7 nM and 2 nM, respectively. In hypoxic lung cancer H460 cells, BAY-87-2243 suppresses HIF target gene expression, and inhibits HIF-1α protein accumulation. BAY-87-2243 showed dose-dependent in vivo antitumor efficacy in the H460 lung tumor xenograft model accompanied by a suppression of HIF-1a protein and HIF-1 target genes without any signs of toxicity or body weight loss. Further mode-of-action analyses revealed that BAY-87-2243 exerts its effect on the HIF pathway by blocking mitochondrial complex I activity and thereby reducing HIF protein levels under hypoxia. BAY-87-2243 had been in phase I clinical trials by Bayer for the treatment of malignancies. However, this study has been terminated for the drug-related adverse events.