Protease-activated receptor 4 (PAR4) (PAR4)

Protease-activated receptor 4 (PAR4), also known as coagulation factor II receptor-like 3 (F2RL3), is a G protein-coupled receptor (GPCR) that serves as a secondary, low-affinity receptor for thrombin on human platelets (UniProt: P55085). While PAR1 initiates platelet activation at low thrombin concentrations, PAR4 is required for the sustained signaling necessary for stable thrombus formation and clot retraction (PubMed: 29439010). Activation occurs when thrombin cleaves the N-terminal domain of the receptor, revealing a tethered ligand that auto-activates the GPCR (NCBI Gene ID: 9002). Because PAR4 is primarily involved in the later stages of thrombosis rather than initial hemostasis, it is a high-interest target for antithrombotic therapy, as its inhibition may offer a lower risk of bleeding compared to PAR1 antagonists or P2Y12 inhibitors (PubMed: 30135131). BMS-986141 is a selective, reversible, small-molecule antagonist of PAR4 developed to prevent arterial thrombosis in patients with cardiovascular disease (ClinicalTrials.gov: NCT02671461).

Other names

Coagulation factor II receptor-like 3F2RL3Thrombin receptor-like 3

BMS-986141 acts as a selective, reversible, small-molecule antagonist of the Protease-activated receptor 4 (PAR4). It works by binding to the receptor and preventing the tethered ligand, created by thrombin cleavage, from interacting with the receptor's binding pocket, thereby inhibiting thrombin-induced platelet aggregation (PubMed: 29439010).