FR 171113

FR171113 is a specific and non-peptide thrombin receptor antagonist. FR171113 exhibits the antithrombotic effects of a PAR1 antagonist. FR171113 inhibits thrombin-induced platelet aggregation with an IC50 of 0.29 μM.[1][2][3][4].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Protease-Activated Receptor (PAR)

FR171113 shows antiplatelet effect on the aggregation of guinea pig platelets induced by PAR1 agonist peptide and thrombin in vitro with IC50s of 1.5 and 0.35 μM, respectively[2]. FR171113 (0.032-1 μM) dose-dependently inhibits platelet aggregation induced by both thrombin and TRAP-6[1]. FR171113 significantly prevents the plasma-elicited up-regulation of RAGE, MCP-1 and ICAM-1 mRNA levels in HUVECs[2]. FR171113 (1 μM; pretreatment for 30 minutes) inhibits thrombin- and SFLLRN (human PAR1 agonist peptide)-induced ERK activation, but not factor Xa- or SLIGKV (PAR2 agonist peptide)-induced ERK activation, indicating that activation of ERK by factor Xa is specifically mediated by PAR2 in mesangial cells[3]. Cell Viability Assay[1] Cell Line: Human washed platelets Concentration: 0.001, 0.01, 0.1, 1, 10, 100 μM Incubation Time: Result: The IC50 value for thrombin-induced platelet aggregation was 0.29 μM. The IC50 value for TRAP-6-induced platelet aggregation was 0.15 μM. RT-PCR[2] Cell Line: human umbilical vein endothelial cells (HUVECs) Concentration: 1 μM Incubation Time: 4 hours Result: 3% citrated human plasma-evoked ROS generation, RAGE, MCP-1 and ICAM-1 gene induction was significantly blocked. Western Blot Analysis[3] Cell Line: Mesangial cells Concentration: 1 μM Incubation Time: Pretreatment for 30 minutes Result: Pretreatment inhibited thrombin (10 nM; for 5 minutes)- and SFLLRN(100 μM for 5 minutes)-induced ERK activation.

FR171113 suppresses occlusive thrombosis dose dependently and causes significant prolongation at 1 mg/kg s.c. in the carotid artery thrombosis model.FR171113 shows antiplatelet and antithrombotic effects in vivo. FR171113 is a useful agent for investigating antithrombotic actions via PAR1 in vivo[4]. Animal Model: Male Hartley guinea pigs (650–950 g) were anesthetized with urethane (1.25 g/kg, i.p.)[4] Dosage: 0.32, 1.0, and 3.2 mg/kg Administration: Administered subcutaneously (s.c.) Result: Pretreatment with FR171113 prolonged this parameter in a dose-dependent manner. The time to thrombotic occlusion for 0.32, 1.0 and 3.2 mg/kg of FR171113 was 30.7±5.36, 44.7±8.41 and 92.6±9.79, respectively.

[1]. Y Kato, et al. In vitro antiplatelet profile of FR171113, a novel non-peptide thrombin receptor antagonist. Eur J Pharmacol. 1999 Nov 19;384(2-3):197-202.

[2]. Yuji Ishibashi, et al. Advanced glycation end products potentiate citrated plasma-evoked oxidative and inflammatory reactions in endothelial cells by up-regulating protease-activated receptor-1 expression. Cardiovasc Diabetol. 2014 Mar 13;13:60.

[3]. Misa Tanaka, et al. Role of coagulation factor Xa and protease-activated receptor 2 in human mesangial cell proliferation. Kidney Int. 2005 Jun;67(6):2123-33.

[4]. Yasuko Kato, et al. Inhibition of arterial thrombosis by a protease-activated receptor 1 antagonist, FR171113, in the guinea pig. Eur J Pharmacol. 2003 Jul 25;473(2-3):163-9.