title: Thrombin receptor antagonists as novel therapeutic targets.
abstract: In addition to its pivotal role in hemostasis, thrombin activates various cell types such as platelets and vascular smooth muscle cells via proteolytic processing of specific cell-surface receptors known as proteinase activated receptors (PARs), the prototype of which is PAR-1. Thrombin receptor activation is likely to play a key role in cardiovascular disorders such as arterial thrombosis, atherosclerosis and restenosis, and as such a thrombin receptor antagonist should have potential utility in the treatment of these disorders. Since the fibrin pathway is unaffected by thrombin receptor antagonism, a thrombin receptor antagonist is expected to have minimal bleeding liability, which is a complicating factor in existing antithrombotic therapy. The currently available collection of thrombin receptor antagonists fall into three categories: (i) peptide antagonists; (ii) peptidomimetics; and (iii) non-peptide thrombin receptor antagonists, and this review outlines the development of members of these classes.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. samuel.chackalamannil@spcorp.com
authors.forename: S
authors.initials: S
authors.lastname: Chackalamannil
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D018179:Receptors, Thrombin