Ferrous Iron-Dependent Pharmacology

The recent emergence of oxidation state selective probes of cellular iron has produced a more nuanced understanding of how cells utilize this crucial nutrient to empower enzyme function, and also how labile ferrous iron contributes to iron-dependent cell death (ferroptosis) and other disease pathologies including cancer, bacterial infections, and neurodegeneration. These findings, viewed in light of the Fenton chemistry promoted by ferrous iron, suggest a new category of therapeutics exhibiting ferrous iron-dependent pharmacology. While still in its infancy, this nascent field draws inspiration from the remarkable activity and tremendous clinical impact of the antimalarial artemisinin. Here, we review recent insights into the role of labile ferrous iron in biology and disease, and describe new therapeutic approaches designed to exploit this divalent transition metal.

Automated summary

The recent emergence of oxidation state selective probes for cellular iron has led to a more nuanced understanding of its role in enzyme function and iron-dependent cell death. These findings suggest new therapeutics targeting ferrous iron and draw inspiration from the success of artemisinin in malaria treatment.