G-protein coupled receptor antagonists-1: protease activated receptor-1 (PAR-1) antagonists as novel cardiovascular therapeutic agents.
Inhibition of thrombin receptor (PAR-1) is a promising therapeutic approach for the treatment of various cardiovascular disorders such as unstable angina, acute myocardial infarction, stroke, and restenosis. Since a PAR-1 antagonist is specific for the cellulalr actions of thrombin, and does not interfere with fibrin generation, it is expected to have less bleeding liability than the currently available treatments. Several peptide and non-peptide PAR-1 antagonists with potent inhibition of platelet aggregation have been reported. Antithrombotic effect of a PAR-1 antibody has been demonstrated in a baboon thrombosis model and the antirestenosis property of a PAR-1 antagonist has been demonstrated in a rat model.
Chackalamannil
Samuel
S
Chemical Research, Schering-Plough Research Institute, Galloping Hill Road, Kenilworth, NJ 07033, USA. samuel.chackalamannil@spcorp.com
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D010215:Papio; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D005343:Fibrinolytic Agents; D010455:Peptides; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin