Bifunctional Ionophores for Cuproptosis Activation: Dual Targeting of Copper and Fe-S Protein Homeostasis.
Cellular resilience to therapy often arises from adaptive mechanisms that safeguard iron-sulfur (Fe-S) proteins. Here, we present a rational strategy to overcome such resilience by integrating two synergistic vulnerabilities, copper toxicity and Fe-S cluster homeostasis, into a single molecular scaffold. Inspired by a...