Agents targeting multiple steps of mitochondrial mechanism have been evaluated in early phase clinical trials. Agents that augment production of reactive oxygen species include mangafodipir/calmangafodipir, motexafin, ARQ-501, ele-sclomol, arsenic trioxide, STA-4783, 2-ME, ENMD-1198, and ATN-224. Other agents affect mitochondrial metabolism via alternate routes, including phenylethyl isothiocyanate downregulation of glutathione, buthionine sulphoximine inhibition of GSH synthesis, and imexon depletion of GSH via thiol binding.
GSH: Reduced glutathione; GSR: Glutathione reductase; GSSG: Glutathione disulfide; H2O: Water; H2O2: Hydrogen peroxide; O2: Oxygen; ROS: Reactive oxygen species; SOD: Superoxide dismutase.