Coagulation factor II receptor-like 3 (PAR4) (PAR4)

Coagulation factor II receptor-like 3, commonly known as Protease-activated receptor 4 (PAR4), is a member of the G protein-coupled receptor (GPCR) family that plays a critical role in platelet physiology (UniProt Q96RI0) [1]. It is activated by the proteolytic cleavage of its N-terminal extracellular domain by thrombin, exposing a tethered ligand that initiates intracellular signaling (PubMed: 30530517) [2]. In human platelets, PAR4 serves as a low-affinity thrombin receptor that complements the high-affinity PAR1, mediating late-stage, sustained platelet activation and the formation of stable thrombi (PubMed: 29133245) [3]. Because PAR4 requires higher concentrations of thrombin for activation, it is considered a promising therapeutic target for antiplatelet therapy, potentially offering a lower risk of bleeding compared to PAR1 antagonists (PubMed: 31434677) [4]. Dysregulation of PAR4 signaling is implicated in cardiovascular diseases such as myocardial infarction and stroke, as well as inflammatory processes. Current drug development efforts focus on small-molecule PAR4 antagonists, such as BMS-986120, to prevent arterial thrombosis while maintaining hemostatic balance [3]. These antagonists work by blocking the interaction between the tethered ligand and the receptor, thereby preventing the secondary wave of platelet aggregation. Clinical studies are evaluating whether PAR4 inhibition can provide superior efficacy or safety compared to existing antiplatelet standards of care.

Other names

Protease-activated receptor 4Proteinase-activated receptor 4F2RL3Thrombin receptor-like 3

Antagonism of the receptor to inhibit thrombin-induced platelet aggregation and stable thrombus formation.