The enzymatic activity of human cytotoxic T-lymphocyte granzyme A and cytolysis mediated by cytotoxic T-lymphocytes are potently inhibited by a synthetic antiprotease, FUT-175

Arch Biochem Biophys. 1991 Jan;284(1):215-8. doi: 10.1016/0003-9861(91)90286-r.


The synthetic antiprotease, FUT-175 (6-amidino-2-naphthyl-4-guanidinobenzoate), was found to be an extraordinarily potent and rapid inhibitor of human Q31 cytotoxic T-lymphocyte granzyme A. The granzyme A was inhibited in a time-dependent manner with kobs/i = 430,000 +/- 80,000 M-1 s-1. Four other FUT-175 analogs were also found to be potent, rapid Q31 granzyme A inhibitors. All five compounds inhibited Q31 cytotoxic T-lymphocyte-mediated cytolysis of human JY lymphoma cells, but at concentrations far in excess of those needed for granzyme A inhibition. The data presented suggest that postmarketing surveillance of FUT-175 should include a review of possible immunosuppressive side-effects, such as increased susceptibility to viral infections and to neoplastic transformations.

MeSH terms

  • Benzamidines
  • Cytotoxicity, Immunologic
  • Granzymes
  • Guanidines / pharmacology*
  • Humans
  • Immunity, Cellular
  • In Vitro Techniques
  • Kinetics
  • Serine Endopeptidases*
  • Serine Proteinase Inhibitors*
  • Structure-Activity Relationship
  • T-Lymphocytes, Cytotoxic / immunology*


  • Benzamidines
  • Guanidines
  • Serine Proteinase Inhibitors
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human
  • nafamostat