title: The history of Z-VAD-FMK, a tool for understanding the significance of caspase inhibition.
abstract: Dr. Robert Smith is one of the pioneers in histochemistry. One of his most important achievements is the recognition of proteolysis as a major physiological and pathophysiological process. As a consequence, he developed selective fluorogenic and chromogenic substrates and specific inhibitors of proteases that allow the (histochemical) analysis of protease activity. One of the latest successes is the design of Z-VAD-fluoromethylketone (FMK), the specific caspase inhibitor, that is a key compound for studies on apoptosis. Its development was originally meant for therapeutic use but unforeseen cytotoxicity of a metabolic derivative of the FMK compound disabled its potential as a drug. However, as a tool for fundamental research it is a great success. The history of Z-VAD-FMK is an example of the creative brain and the tireless perseverance of Robert Smith for which histochemistry and cytochemistry owes him so much. This history of Z-VAD-FMK is a well-deserved tribute at the occasion of his 70th birthday.
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Noorden
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000266:history* / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000266:history / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000266:history / Q000378:metabolism; D015195:Drug Design; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases