Inhibitors of protease-activated receptor 4 (PAR4): a review of recent patents (2013-2021)

Abstract

Introduction: Protease-activated receptor 4 (PAR4), belonging to a subfamily of G-protein-coupled receptors (GPCR), is expressed on the surface of Human platelets, and the activation of it can lead to platelets aggregation. Studies demonstrated that PAR4 inhibition protect mice from arterial/arteriolar thrombosis, pulmonary embolism and cerebral infarct, while do not affect the hemostatic responses integrity. Therefore, PAR4 has been a promising target for the development of anti-thrombotic agents.

Areas covered: This review covers recent patents and literature on PAR4 and their application published between 2013 and 2021.

Expert opinion: PAR4 is a promising anti-thrombotic target and PAR4 inhibitors are important biologically active compounds for the treatment of thrombosis. Most the recent patents and literature focus on PAR4 selective inhibitors, and BMS-986120 and BMS-986141, which were developed by BMS, have entered clinical trials. With the deep understanding of the crystal structures and biological functions of PAR4, we believe that many other novel types of molecules targeting PAR4 would enter the clinical studies or the market.

Keywords: PAR4; Protease-activated receptor 4; anti-platelet; anti-thrombosis; antibody; small-molecule antagonists.