Protease-activated receptor 1 (PAR1) (PAR1)

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR) that serves as the primary high-affinity receptor for thrombin on human platelets and endothelial cells [1, 5]. It is characterized by a unique activation mechanism in which a protease, typically thrombin, cleaves the receptor's N-terminal extracellular domain to reveal a "tethered ligand" that intramolecularly activates the receptor [1, 14]. PAR1 plays a critical role in hemostasis and thrombosis by mediating thrombin-induced platelet aggregation and shape change [5, 6]. Beyond its role in coagulation, PAR1 is involved in inflammatory responses, vascular development, and endothelial barrier maintenance through biased signaling pathways [7, 15]. In oncology, PAR1 is often overexpressed in various cancers, including breast and lung cancer, where it promotes tumor cell invasion, migration, and metastasis [8, 11]. While PAR1 is a validated therapeutic target for preventing cardiovascular events, its clinical use is limited by a significant risk of major bleeding, particularly intracranial hemorrhage [3, 16].

Other names

Coagulation factor II receptorThrombin receptorF2RProteinase-activated receptor 1CHTRTRHTRCF2R

Protease-activated receptor 1 antagonist, Thrombin receptor antagonist, Allosteric modulation, Biased signaling modulation