Caspases: Structure-Guided Design of Drugs to Control Cell Death

The structures of caspases reveal the mechanism of binding for non-peptide and protein inhibitors, and have been applied in the design of agents that either inhibit or activate caspases to control cell death in diverse diseases. Decreased cell death is desirable for treatment of stroke, nerve crush injury, myocardial infarction, neuromuscular and neurodegenerative diseases and several non-peptide caspase inhibitors have been developed. In contrast, activation of cell death would be advantageous in cancer therapy, and the strategy is to block the binding of inhibitory proteins to caspases. Recent preclinical studies are described.