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[11] The overall arc is a compound that engaged its target as designed but repeatedly failed to convert that biochemical effect into approved clinical benefit, and accumulated tolerability concerns along the way

Under physiological conditions, the main intracellular sources of ROS include the mitochondrial electron transport chain, NADPH oxidases (NOX), xanthine oxidase and various endoplasmic reticulum and peroxisomal oxidoreductases

in this work he ascribed the beneficial effects of these molecules to a pro-oxidant effect that underlies adaptive responses in what could be defined as a para-hormetic mechanism involving radical signalling