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.
Weber
Irene T
IT
Department of Biology, Georgia State University, P.O. Box 4010, Atlanta, GA 30302, USA. iweber@gsu.edu
Fang
Bin
B
Agniswamy
Johnson
J
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D020536:Enzyme Activators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D013379:Substrate Specificity
D061945:Caspase Inhibitors; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D020169:Caspases