Researchers at the University of California, Davis have discovered a class of compounds that both bind to a unique newly-discovered binding site in respiratory complex III and act as inhibitors of electron transport for use as mitochondrial anti-cancer drugs.
Higher basal levels of reactive oxygen species (ROS) in cancer cells make them susceptible to ROS-induced apoptosis. A major producer of ROS in the mitochondrial electron transport chain (METC), respiratory complex III is a natural target for anticancer drugs. Current inhibitors of respiratory complex III promote ROS production by competitively out binding natural ligands, necessitating a relatively high dosage level causing attendant off-target effects.
Researchers at the University of California, Davis have discovered a class of METC inhibitors that bind to a unique binding site within respiratory complex III. Inhibition of the METC increases ROS production in cancer cells triggering apoptosis. Due to natural ligands low affinity for this binding site, the effective dosage for these compounds is lower than current METC inhibitors, resulting in fewer side effects.
respiratory complex III, switch, ROS, mitochondrial electron transport chain, METC, anti-cancer