A finding of highly selective synthetic inhibitor of plasma kallikrein; its action to bradykinin generation, intrinsic coagulation and experimental DIC.
We found a novel and highly selective synthetic inhibitor of plasma kallikrein (PK), called PKSI-527; the Ki value was 0.81 microM. PKSI-527 inhibited the bradykinin (BK) generation induced by kaolin and prolonged partial thromboplastin time (PTT). PKSI-527 prevented the decrease of fibrinogen (Fg) levels due to i.v. injection of ellagic acid in mice and ameliorated the endotoxin (ET)-induced DIC in rats.
Okamoto
S
S
Kobe Research Projects on Thrombosis and Haemostasis, Japan.
Wanaka
K
K
Hijikata-Okunomiya
A
A
Okada
Y
Y
Katsuura
Y
Y
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001920:Bradykinin / Q000096:biosynthesis; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000517:prevention & control; D004731:Endotoxins / Q000633:toxicity; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D007616:Kaolin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010314:Partial Thromboplastin Time; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D004731:Endotoxins; C064866:PKSI 527; D007616:Kaolin; D010649:Phenylalanine; D014148:Tranexamic Acid; D005340:Fibrinogen; D007610:Kallikreins; D001920:Bradykinin