PDP1 and neoplasm: CPI-613, a lipoate analogue that blocks pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH), inhibiting mitochondrial metabolism: CPI-613 induces PDH inactivating phosphorylation via stimulation of PDK, inducing a consequent collapse of mitochondrial function and the activation of multiple tumor cell death pathways; in parallel, CPI-613 induces a large, tumor-specific production of mitochondrial ROS from the E3 subunit of KGDH, inducing an inhibition of this enzyme [197].