Developing PAR1 antagonists: minding the endothelial gap

Discov Med. 2012 Jun;13(73):425-31.


Proteinase Activated Receptors (PARs) are G-protein coupled receptors (GPCRs) that were discovered in the early 1990's. They are unusual among GPCRs in being activated through proteolytic cleavage of the receptor N-terminus by serine proteinases such as thrombin. Over the last two decades major advances have been made in our understanding of how these receptors function and the roles they play in (patho)physiology. They have also emerged as drug targets for a number of conditions, most notably thrombosis. Recently two different drugs targeting PAR1 have entered clinical trials as anti-platelet agents. This review provides an overview of the proteinase activated receptor family and focuses on the role of PAR1 in regulating the endothelial barrier integrity and its implication on developing PAR antagonists for anti-platelet therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Humans
  • Lactones / therapeutic use
  • Platelet Aggregation Inhibitors / therapeutic use
  • Pyridines / therapeutic use
  • Receptors, Proteinase-Activated / antagonists & inhibitors*
  • Receptors, Proteinase-Activated / metabolism*
  • Thrombosis / drug therapy


  • Lactones
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Receptors, Proteinase-Activated
  • vorapaxar