Estrogen-related receptor α (ERRα) inverse agonist (IC50 value of ~300–500 nM) and potent mitochondrial uncoupler that induces cell death in chemotherapeutic resistant cancer cells by causing mitochondrial dysfunction. XCT790 was found to potently activate AMPK in a dose-dependent and ERRα-independent manner at concentrations more than 25-fold below those typically used to perturb ERRα. Measurements of mitochondrial membrane potential, oxygen consumption, and extracellular acidification rates indicated acute and dose-dependent uncoupling of oxidation from phosphorylation in mitochondria by XCT 790. It modulates the activity of ERRα and reduces the proliferation of various cell lines by blocking the G1/S transition of the cell cycle in an ERRα-dependent manner. XCT 790 showed no activity towards a wide range of (GAL4-chimeric) receptors.