Lipoic acid is a natural organosulfur compound that serves as a cofactor in various complexes, including the α-ketoglutarate dehydrogenase complex, which is involved in the citric acid cycle as well as other pathways. CPI-613 is a lipoic acid analog that inhibits α-ketoglutarate dehydrogenase, particularly in tumor cells. At 60-240 μM, CPI-613 induces a strong mitochondrial burst of reactive oxygen species, resulting in cell death. By disrupting mitochondrial metabolism, CPI-613 demonstrates both in vitro and in vivo anti-tumor activity through both apoptotic and non-apoptotic pathways.
