title: Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32.
abstract: Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases.
authors.affiliation: MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester, U.K.
authors.forename: E A
authors.initials: EA
authors.lastname: Slee
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: S C
authors.initials: SC
authors.lastname: Chow
authors.forename: M
authors.initials: M
authors.lastname: MacFarlane
authors.forename: D W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: G M
authors.initials: GM
authors.lastname: Cohen
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology / Q000473:pathology; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000473:pathology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011480:Protease Inhibitors; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases