thrombin receptors

Vorapaxar (MK-5348) (SCH 530348) is an effective and orally active thrombin receptor (PAR-1) antagonist (Ki: 8.1 nM).

Atopaxar, a reversible PAR-1 thrombin receptor antagonist, interferes with platelet signaling. Atopaxar has been investigated for the treatment of Coronary Artery Disease and Acute Coronary Syndrome.

Atopaxar (E5555), a reversible PAR-1 thrombin receptor antagonist, interferes with platelet signaling. Atopaxar has been investigated for the treatment of Coronary Artery Disease and Acute Coronary Syndrome.

Parmodulin 2 (ML 161) is the inhibitor of protease-activated receptor 1 (PAR1)-mediated platelet activation (IC50: 0.26 μM for the inhibition of platelet P-selectin expression on human platelets). It also inhibits thrombin-induced platelet activation.

AC-55541 (AOB2796) is a novel PAR2 agonist; activated PAR2 signaling in cellular proliferation assays, phosphatidylinositol hydrolysis assays, and Ca(2+) mobilization assays, with potencies ranging from 200 to 1000 nM.

SCH79797 dihydrochloride is an effective and selective antagonist of protease activated receptor 1 (PAR1) with an IC50 of 70 nM and a Ki of 35 nM. SCH79797 dihydrochloride has antiproliferative and pro-apoptotic effects.

Protease-Activated Receptor-4 (PAR4) is a proteinase-activated receptor-4 agonist used in antiplatelet therapy.

12(S)-HETrE is an endogenous metabolite produced by oxidation of ω-6 PUFA dihomo-γ-linolenic acid (DGLA) by 12-lipoxygenase (12-LOX) in platelets, which acts on Gαs-coupled G-protein-coupled receptors, has antithrombotic properties, and has potential therapeutic use in cardiovascular disease. 12(S)-HETrE is reported to inhibit agonist-mediated platelet activation (IC50 = 40 μM), α granule secretion, integrin αIIbβ3 activation, Rap1 activation, and thrombin-induced clot retraction in vitro.

Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2 is a biologically active peptide functioning as a selective agonist for Protease Activated Receptor 1 (PAR-1) [a subtype of G-protein coupled receptors involved in mediating thrombin's cellular effects]. Exhibiting high specificity for PAR-1 over PAR-2, its selectivity was assessed via cell-based calcium signaling assays in HEK293 cells. As an agonist, it is instrumental for in vivo investigations of PAR-1 activation. PAR-1 also collaborates with PAR-4, influencing thrombin-induced hepatocellular carcinoma within [coagulation type] tumor environments where thrombin generation occurs.

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

PAR-2-IN-1 (IUN76750) is a PAR- 2 signaling pathway inhibitor with anti-inflammatory and anticancer effects.

AC-264613 is an agonist of the GPCR protease-activated receptor 2 (PAR2). AC-264613(AC264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages. AC-264613(AC264613) activated PAR2 signaling in cellular proliferation assays, phosphatidylinositol hydrolysis assays, and Ca(2+) mobilization assays, with potencies ranging from 30 to 100 nM.

AZ3451 is an allosteric antagonist of protease-activated receptor-2 (PAR2, IC50: 23 nM).

Vorapaxar sulfate (Zontivity) is a potent and orally active thrombin receptor (PAR-1) antagonist.

PAR-4 Agonist Peptide, amide TFA (PAR-4-AP (TFA)), is a selective activator of the proteinase-activated receptor-4 (PAR-4) that does not affect PAR-1 or PAR-2, and its activity can be inhibited by a PAR-4 antagonist.

SLIGRL-NH2 (Protease-Activated Receptor-2 Activating Peptide) is a PAR-2 agonist that induces non-histaminergic pruritus.

I-191 is a potent antagonist of protease-activated receptor 2 (PAR2), inhibits multiple signaling functions in human cancer cells.

Psychotridine is an alkaloid that has been found inP. forsterianaand has diverse biological activities.1,2,3It inhibits ADP-, collagen-, or thrombin-induced aggregation of washed isolated human platelets with IC50values of 1.4, 1.4, and 3.9 μM, respectively.1Psychotridine (2.5 or 5 μM) is cytotoxic to HTC rat hepatocellular carcinoma cells.2It reduces paw licking induced by capsaicin in mice when administered at doses of 0.5, 2.5, or 5 mg/kg.3 1.Beretz, A., Roth-Georger, A., Corre, G., et al.Polyindolinic alkaloids from Psychotria forsteriana. Potent inhibitors of the aggregation of human plateletsPlanta Med.51(4)300-303(1985) 2.Roth, A., Kuballa, B., Bounthanh, C., et al.Cytotoxic activity of polyindoline alkaloids of Psychotria forsteriana (Rubiaceae) (1)Planta Med.6450-453(1986) 3.Amador, T.A., Verotta, L., Nunes, D.S., et al.Involvement of NMDA receptors in the analgesic properties of psychotridinePhytomedicine8(3)202-206(2001)

Protease-Activated Receptor-2, amide (SLIGKV-NH2) is an agonist of PAR2 with an IC50 of 10.4 M.