CPI-613 is a non-redox active lipoate derivative that acts as a selective inhibitor mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase. In vitro, CPI-613 dose-dependently and efficiently kills H460 human lung cancer cells and Saos-2 human sarcoma cells. In vitro, CPI-613 treatment potently disrupts H460 cancer cell mitochondrial metabolism including inhibition of PDH complex activity. CPI-613 treatment also leads to loss of mitochondrial membrane potential as assessed by JC-1 mitochondrial uptake. CPI-613 also induces apoptotic and non-apoptotic cell death in the cells of H460 human lung cancer and Saos-2 human sarcoma in vitro.