In vitro effects of inogatran, a selective low molecular weight thrombin inhibitor.
The thrombin inhibitor inogatran is a synthetic peptidomimetic with a molecular weight of 439 dalton. In vitro studies have shown that inogatran is a classical competitive inhibitor of the active site of thrombin with a Ki of 15 x 10(-9) mol/l. Inogatran doubles the thrombin clotting time in human plasma at 20 x 10(-9) mol/l, APTT at 1.2 x 10(-6) mol/l, and prothrombin time at 4 x 10(-6) mol/l. The effects on rat and dog plasma are similar although slightly weaker. IC50 for inhibition of thrombin-induced aggregation of human platelets is 17 x 10(-9) mol/l. Inogatran has no effect on platelet aggregation induced by ADP or collagen. Up to a concentration of 10 x 10(-6) mol/l inogatran does not inhibit t-PA-induced fibrinolysis as seen in an ECLT system. Inogatran has good selectivity for thrombin as compared to several other serine proteases occurring in the blood. It is concluded that the properties of inogatran in vitro make the compound suitable for further studies in animals and man.
Teger-Nilsson
A C
AC
Astra Hässle AB, Mölndal, Sweden.
Bylund
R
R
Gustafsson
D
D
Gyzander
E
E
Eriksson
U
U
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004285:Dogs; D005342:Fibrinolysis; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases; D013917:Thrombin / Q000494:pharmacology; D013918:Thrombin Time
D000991:Antithrombins; D010880:Piperidines; C099871:inogatran; D000244:Adenosine Diphosphate; D003094:Collagen; D012697:Serine Endopeptidases; D013917:Thrombin; D005998:Glycine