Inhibitory Effect of a New Synthetic Protease Inhibitor (FUT-175) on the Coagulation System

Abstract
The inhibitory effects of 6-amidino-2-naphthyl-4-guanidinobenzoate .cntdot. dimethanesulfonate (FUT-175) on the human Hageman factor fragment (HFf), factor Xa, thrombin, plasma kallikrein, and plasmin were studied. FUT-175 inhibited plasma kallikrein most (IC50 [concentration producing 50% inhibition] = 3.0 .times. 10-9 M), followed by HFf (IC50 = 3.3 .times. 10-7 M). FUT-175 had an anticoagulant effect in the APTT [activated partial thromboplastin time] and PT [prothrombin time] assay systems of human plasma. The concentration of FUT-175 for 2-fold increase in the clotting time in the APTT assay system was 5 .times. 10-7 M.