Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit.

The indispensable requirement for metals in life processes has led to the evolution of sophisticated mechanisms that allow organisms to maintain dynamic equilibria of these ions. This dynamic control of the level, speciation, and availability of a variety of metal ions allows organisms to sustain biological processes while avoiding toxicity. When functioning properly, these mechanisms allow cells to return to their metal homeostatic set points following shifts in the metal availability or other stressors. These periods of transition, when cells are in a state of flux in which they work to regain homeostasis, present windows of opportunity to pharmacologically manipulate targets associated with metal-trafficking pathways in ways that could either facilitate a return to homeostasis and the recovery of cellular function or further push cells outside of homeostasis and into cellular distress. The purpose of this Viewpoint is to highlight emerging opportunities for chemists and chemical biologists to develop compounds to manipulate metal-trafficking processes for therapeutic benefit.