Taming glutathione potentiates metallodrug action

Metallodrugs that are redox sensitive or have labile coordina-tion sites are particularly susceptible to inhibition by gluta-thione (GSH) and other endogenous thiols. Because GSH is an essential antioxidant, strategies to prevent thiol deactivation must consider their potential effects on normal cellular func-tions. In this short review, we describe general approaches for taming glutathione in metallodrug therapy and discuss their strengths and limitations. We also offer our perspectives on developing practical solutions that are effective and clinically relevant.