PAR1
Protease-activated receptor 1 (PAR1) is a proteolytically activated GPCR that links thrombin or PAR1-selective agonist stimulation to cellular signaling programs in platelets, neurons, astrocytes, fibroblasts, endothelial cells, and kidney cells[1][2][3]. Mechanistically, PAR1 couples to Gq/11, Gi/o, and G12/13 pathways, while discrete residues in its second intracellular loop selectively control Gq/11-dependent inositol phosphate and calcium signaling[4]. In neurons, PAR1 activation drives 2-arachidonoylglycerol retrograde signaling, activates presynaptic CB1 receptors, and suppresses inhibitory synaptic transmission[2]. In inflammatory and injury models, thrombin-PAR1 signaling promotes astrocyte proliferation, reverses stellation, inhibits migration, and activates MAPK/NFκB inflammatory responses after spinal cord injury[1]. PAR1 also contributes to tissue remodeling, because thrombin and the PAR1 agonist TFLLR stimulate fibroblast-mediated collagen gel contraction through PAR1 and PKC-ε[3]. Compared with PAR4, PAR1 in human platelets shows homologous desensitization, whereas PAR4 signaling can restore PAR1-dependent aggregation through PKC-mediated granule release[5]. For experimental applications, PAR1 agonists such as TFLLR or SFLLRN model receptor activation, while inhibitors such as dabigatran, SCH79797, and PZ-128 help dissect thrombin cleavage, receptor signaling, platelet biology, and vascular disease mechanisms[6][7][8].
References:
- [1]. Chen X, et al. Thrombin induces morphological and inflammatory astrocytic responses via activation of PAR1 receptor. Cell Death Discov. 2022 Apr 11;8(1):189. [Content Brief]
- [2]. Hashimotodani Y, et al. Neuronal protease-activated receptor 1 drives synaptic retrograde signaling mediated by the endocannabinoid 2-arachidonoylglycerol. J Neurosci. 2011 Feb 23;31(8):3104-9. [Content Brief]
- [3]. Fang Q, et al. Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-epsilon. Eur Respir J. 2004 Dec;24(6):918-24. [Content Brief]
- [4]. McCoy KL, et al. Protease-activated receptor 1 (PAR1) coupling to G(q/11) but not to G(i/o) or G(12/13) is mediated by discrete amino acids within the receptor second intracellular loop. Cell Signal. 2012 Jun;24(6):1351-60. [Content Brief]
- [5]. Fälker K, et al. Protease-activated receptor 1 (PAR1) signalling desensitization is counteracted via PAR4 signalling in human platelets. Biochem J. 2011 Jun 1;436(2):469-80. [Content Brief]
- [6]. Chen B, et al. Characterization of thrombin-bound dabigatran effects on protease-activated receptor-1 expression and signaling in vitro. Mol Pharmacol. 2015 Jul;88(1):95-105. [Content Brief]
- [7]. Di Serio C, et al. Protease-activated receptor 1-selective antagonist SCH79797 inhibits cell proliferation and induces apoptosis by a protease-activated receptor 1-independent mechanism. Basic Clin Pharmacol Toxicol. 2007 Jul;101(1):63-9. [Content Brief]
- [8]. Kuliopulos A, et al. PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2990-3003. [Content Brief]
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PAR1 Related Products (33)
Related Products (33)
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Murine Thrombin
0 ImagesCat. No.: HY-114164GCAS No.: 9002-04-4Murine Thrombin is a murine serine protease that plays a central role in blood coagulation. Murine Thrombin stimulates macrophages to polarize into a unique phenotype characterized by anti-inflammatory and pro-repair properties. Murine Thrombin activates PAR1, induces the production of MCP-1, MMP3 and VEGF in mouse intervertebral discs, and causes degradation of the cartilage matrix and destruction of intervertebral disc structure. Murine Thrombin activity increases significantly in paraoxon-induced status epilepticus.
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Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2 TFA
0 ImagesCat. No.: HY-P5372APurity: 99.78%Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2 TFA, a bioactive peptide, is a selective Protease activating receptor 1 (PAR-1) agonist over PAR-2. PAR-1 belongs to a subfamily of G-protein coupled receptors and is known to mediate the cellular effects of thrombin. In addition to its varied cellular effects of thrombin, PAR-1 has also been shown to coordinate with PAR-4 and regulate thrombin-induced hepatocellular carcinoma harboring thrombin formation within the tumor environment classified as 'coagulation type'.
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Canine Thrombin
0 ImagesCat. No.: HY-114164FCAS No.: 9002-04-4Canine Thrombin is a Canine serine protease that plays a central role in blood coagulation. Canine Thrombin stimulates macrophages to polarize into a unique phenotype characterized by anti-inflammatory and pro-repair properties. Canine Thrombin activates PAR1, induces the production of MCP-1, MMP3 and VEGF in intervertebral discs, and causes degradation of the cartilage matrix and destruction of intervertebral disc structure. Canine Thrombin activity increases significantly in paraoxon-induced status epilepticus.
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FR-171113
0 ImagesCat. No.: HY-108555CAS No.: 173904-50-2
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SCH-602539
0 ImagesCat. No.: HY-18201CAS No.: 618385-42-5
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PPACK
0 ImagesCat. No.: HY-122542CAS No.: 71142-71-7PPACK is a potent, peptidic inhibitor targeting thrombin and granzyme GZMK. PPACK specifically blocks the activities of thrombin and GZMK, thereby inhibiting thrombin-mediated PAR-1 cleavage, as well as downstream inflammatory and procoagulant signaling pathways. Through stabilizing IκB proteins, blocking NF-κB activation and reducing systemic levels of proinflammatory/procoagulant biomarkers, PPACK exerts multiple effects including anti-inflammatory, antithrombotic, barrier repair, and inhibition of atherosclerotic plaque progression. PPACK binds to platelets without interference from kininogen, effectively limiting acute thrombus growth and reducing eosinophil infiltration and goblet cell hyperplasia in asthma models. PPACK is an important tool molecule for investigating the mechanisms of atherosclerosis, asthma and related thromboinflammatory diseases.
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Atopaxar hydrochloride
0 ImagesCat. No.: HY-18200ACAS No.: 474544-83-7Synonyms: E5555 hydrochloride; ER-172594-00 hydrochlorideAtopaxar hydrochloride (E5555 hydrochloride) is the hydrochloride salt form of Atopaxar (HY-18200). Atopaxar hydrochloride is an orally active, selective and reversible antagonist for thrombin receptor protease-activated receptor-1 (PAR-1). Atopaxar hydrochloride is the inhibitor for Janus kinase 1 (JAK1) and JAK2, which inhibits the JAK-STAT with EC50 of 5.90 μM in A549. Atopaxar hydrochloride inhibits the cell viability of A549 (IC50=7.02 μM), arrests the cell cycle at G1 phase and induces apoptosis. Atopaxar hydrochloride exhibits antiplatelet and antitumor activities. Atopaxar hydrochloride can be used for the research of atherothrombotic disease.
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Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2
0 ImagesCat. No.: HY-P5372CAS No.: 211190-38-4Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2, a bioactive peptide, is a selective Protease activating receptor 1 (PAR-1) agonist over PAR-2. PAR-1 belongs to a subfamily of G-protein coupled receptors and is known to mediate the cellular effects of thrombin. In addition to its varied cellular effects of thrombin, PAR-1 has also been shown to coordinate with PAR-4 and regulate thrombin-induced hepatocellular carcinoma harboring thrombin formation within the tumor environment classified as 'coagulation type'.
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RWJ-56110
0 ImagesCat. No.: HY-108556CAS No.: 252889-88-6RWJ-56110 is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 (HY-108566). RWJ-56110 inhibits angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 induces cell apoptosis.
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Protease-Activated Receptor-1 antagonist 2
0 ImagesCat. No.: HY-143314CAS No.: 1454588-34-1Protease-Activated Receptor-1 antagonist 2 is an orally active protease-activated receptor-1 (PAR-1) antagonist, with an IC50 value of 7 nM. Protease-Activated Receptor-1 antagonist 2 has favorable pharmacokinetic properties which is useful in the research of cardiovascular disease (CVD), such as atherosclerosis and restenosis.
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Atopaxar hydrobromide
0 ImagesCat. No.: HY-18200BCAS No.: 474550-69-1Synonyms: E5555 hydrobromide; ER 172594-06Atopaxar (E5555) hydrobromide is a potent, orally active, selective and reversible thrombin receptor protease-activated receptor-1 (PAR-1) antagonist. Atopaxar hydrobromide, an antiplatelet agent, interferes with platelet signaling. Atopaxar hydrobromide can be used for the research of atherothrombotic disease.
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