24 research outputs found
The inhibition of trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4â˛-nitrobenzyl 4-guanidinobenzoate
AbstractThe inhibition of the enzymes trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4â˛-nitrobenzyl 4-guanidinobenzoate is caused by acylation of the active site. Second order rate constants were determined
Der Einflu� heparin�hnnlicher Substanzen auf die Reaktion zwischen Antithrombin und Thrombin
A novel cellâbased sensor detecting the activity of individual basic proprotein convertases
Urethanyl-3-Amidinophenylalanine Derivatives as Inhibitors of Factor Xa. X-Ray Crystal Structure of a Trypsin/Inhibitor Complex and Modeling Studies
Changing the selectivity profile â from substrate analog inhibitors of thrombin and factor Xa to potent matriptase inhibitors
Protease-Activated Receptor 1-Selective Antagonist SCH79797 Inhibits Cell Proliferation and Induces Apoptosis by a Protease-Activated Receptor 1-Independent Mechanism
Thrombin, a key mediator of blood coagulation, exerts a large number of cellular actions via activation of a specific G-protein-coupled receptor, named protease-activated receptor I (PARI). Several studies in experimental animals have demonstrated a therapeutic potential of small molecules with PARI antagonistic properties for treatment of diseases such as vascular thrombosis and arterial restenosis. We have studied the biological actions of one highly potent, selective PARI antagonist, SCH79797 (N 3-cyclopropyl-7-{[4-(1-methyletbyl)phenyl]methyl}-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), in vitro, and found that this compound was able to interfere with the growth of several human and mouse cell lines, in a concentration-dependent manner. The ED50 for growth inhibition was 75 nM, 81 nM and 116 nM for NIH 3T3, HEK 293 and A375 cells, respectively. Moreover, in NIH 3T3 cells, SCH79797 inhibited serum-stimulated activation of p44/p42 mitogen-activated protein kinases (MAPK) at low concentrations and induced apoptosis at higher concentrations. However, the antiproliferative and pro-apoptotic effects of SCH79797 are likely Dot mediated by PAR1 antagonism, as they were also observed in embryonic fibroblasts derived from PAR1 null mice. These data suggest that, in view of the development of PAR1-selective antagonists as therapeutic agents, effects potentially unrelated to PAR1 inhibition should be carefully scrutinized