Using par4 inhibition as an anti-thrombotic approach: Why, how, and when?

Simeng Li, Volga Tarlac, Justin R. Hamilton

Research output: Contribution to journalReview ArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Protease-activated receptors (PARs) are a family of four GPCRs with a variety of cellular functions, yet the only advanced clinical endeavours to target these receptors for therapeutic gain to date relates to the impairment of platelet function for anti-thrombotic therapy. The only approved PAR antagonist is the PAR1 inhibitor, vorapaxar—the sole anti-platelet drug against a new target approved in the past 20 years. However, there are two PARs on human platelets, PAR1 and PAR4, and more recent efforts have focused on the development of the first PAR4 antagonists, with first-in-class agents recently beginning clinical trial. Here, we review the rationale for this approach, outline the various modes of PAR4 inhibition, and speculate on the specific therapeutic potential of targeting PAR4 for the prevention of thrombotic conditions.

Original languageEnglish
Article number5629
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume20
Issue number22
DOIs
Publication statusPublished - 2 Nov 2019

Keywords

  • Antagonists
  • Anti-platelets
  • Anti-thrombotics
  • Platelet
  • Protease-activated receptors
  • Thrombin
  • Thrombosis

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