Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties

Apoptosis. 2003 Aug;8(4):345-52. doi: 10.1023/a:1024116916932.


In recent years, several inhibitors that prevent caspase activation and apoptosis have emerged. At high doses, however, these inhibitors can have nonspecific effects and/or become cytotoxic. In this study, we determined the effectiveness of broad spectrum caspase inhibitors to prevent apoptosis. A carboxy terminal phenoxy group conjugated to the amino acids valine and aspartate (Q-VD-OPh) potently inhibited apoptosis. Q-VD-OPh was significantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk, and was also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. In addition to the increased effectiveness, Q-VD-OPh was not toxic to cells even at extremely high concentrations. Our data indicate that the specificity, effectiveness, and reduced toxicity of caspase inhibitors can be significantly enhanced using carboxyterminal o-phenoxy groups and may have important uses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / chemistry
  • Amino Acid Chloromethyl Ketones / metabolism
  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Benzyl Compounds / metabolism
  • Benzyl Compounds / pharmacology
  • Caspase Inhibitors*
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • DNA Fragmentation
  • Dactinomycin / metabolism
  • Humans
  • Hydrocarbons, Fluorinated / metabolism
  • Hydrocarbons, Fluorinated / pharmacology
  • Jurkat Cells
  • Mice
  • Nucleic Acid Synthesis Inhibitors / metabolism
  • Quinolines / chemistry
  • Quinolines / metabolism
  • Quinolines / pharmacology*
  • Rats
  • Thapsigargin / metabolism
  • Transforming Growth Factor beta / metabolism


  • Amino Acid Chloromethyl Ketones
  • Benzyl Compounds
  • Boc-D-FMK
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Hydrocarbons, Fluorinated
  • Nucleic Acid Synthesis Inhibitors
  • Quinolines
  • Transforming Growth Factor beta
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • quinoline-val-asp(OMe)-CH2-OPH
  • Dactinomycin
  • Thapsigargin