RWJ-58259
RWJ-58259 is a selective PAR-1 inhibitor with an IC50 value of 0.15 μM. RWJ-58259 binds selectively to PAR-1, blocks the binding of tethered ligands, interferes with calcium mobilization and PAR-1-related cellular functions, and exhibits no PAR-1 agonist activity or thrombin proteolytic inhibitory activity. RWJ-58259 inhibits thrombin-induced platelet aggregation, calcium signaling and vascular smooth muscle cell proliferation, reduces neointimal thickness and arterial stenosis, and alleviates vascular occlusion and platelet deposition. RWJ-58259 can be used in the research of thrombotic diseases and vascular injury associated with acute coronary intervention.
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- CAS No.: 315203-31-7
- Formule: C40H42Cl2F2N8O3
- Masse moléculaire:791.72
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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PAR1 0.15 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| MDA-MB-231 | IC50 |
0.005 μM
Compound: RWJ-58259
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Antagonist activity at PAR1 in human MDA-MB-231 cells assessed as inhibition of TFLLRN-NH2-induced intracellular calcium mobilization preincubated for 15 mins followed by TFLLRN-NH2 addition by Fluo-4-AM dye based fluorescence assay
Antagonist activity at PAR1 in human MDA-MB-231 cells assessed as inhibition of TFLLRN-NH2-induced intracellular calcium mobilization preincubated for 15 mins followed by TFLLRN-NH2 addition by Fluo-4-AM dye based fluorescence assay
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[PMID: 30655958] |
RWJ-58259 potently binds to PAR-1 in the cell membrane of CHRF-288-11, with an IC50 of 0.15 μM[1].
RWJ-58259 potently and selectively inhibits thrombin-induced aggregation (IC50 0.37 μM) and TRAP-6-induced aggregation (IC50 0.11 μM) of gel-filtered platelets, and shows no activity against collagen or U46619 at concentrations up to 50 μM[1].
RWJ-58259 potently inhibits α-thrombin-induced calcium mobilization in RASMC, with an IC50 of 0.07 μM[1].
RWJ-58259 inhibits α-thrombin-induced proliferation of RASMC with an IC50 of 2.3 μM[1].
RWJ-58259 potently inhibits α-thrombin-induced calcium mobilization in hPAR-1-transfected mouse pulmonary myofibroblasts with an IC50 of 0.31 μM; it also inhibits TRAP-6-induced calcium mobilization with an IC50 of 0.11 μM[1].
RWJ-58259 inhibits PAR-1-mediated calcium mobilization in hPAR-1-transfected cells, with an IC50 of 0.31 μM for thrombin-induced signaling pathways and an IC50 of 0.11 μM for SFLLRN-induced signaling pathways[2].
RWJ-58259 inhibits PAR-1-mediated proliferation in thrombin-induced rat vascular smooth muscle cells, with an IC50 of 2.3 μM[2].
RWJ-58259 inhibits thrombin-induced PAR-1-mediated IL-6 release in vascular smooth muscle cells, with an IC50 of 3.6 μM[2].
RWJ-58259 inhibits PAR-1-mediated microvascular growth in rat aortic ring models with an IC50 of 3 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Intravenous infusion of RWJ-58259 maintains plasma concentrations ≥12 μM, significantly prolongs occlusion time, completely prevents vascular occlusion in the tested arteries, reduces platelet-rich thrombus formation in a cynomolgus monkey arterial injury thrombosis model, and does not affect hemostatic parameters[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:unspecified strain[1]
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Dosage:10 mg
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Administration:perivascular; 14-day vascular injury restenosis experiment
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Result:Reduced intimal area to 0.084 mm2 compared to 0.129 mm2 in vehicle controls (p < 0.05).
Reduced percentage stenosis to 26% compared to 44% in vehicle controls (p < 0.05).
Reduced neointimal thickness to 45 μm compared to 77 μm in vehicle controls (p < 0.05).
Reduced intima/media ratio to 0.83 compared to 1.35 in vehicle controls (p < 0.05).
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Animal Model:unspecified strain[1]
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Dosage:A certain dose
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Administration:i.v. infusion
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Result:Attenuated or prevented vessel occlusion in 100% of treated vessels (N=9).
Achieved complete 60-minute patency in 5 out of 9 vessels.
Significantly increased time to occlusion compared to vehicle controls (p < 0.05).
Significantly reduced platelet deposition and shifted thrombi from platelet-rich to platelet-poor.
Caused no significant effects on key hematological or coagulation parameters.
Chemical Information
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CAS No. 315203-31-7
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Masse moléculaire 791.72
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Formule C40H42Cl2F2N8O3
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SMILES
FC(C=C1C[C@@H](C(N[C@@H](CCN)C(NCC2=CC=CC=C2)=O)=O)NC(NC3=CC=C(C(CN4CCCC4)=N5)C(N5CC6=C(C=CC=C6Cl)Cl)=C3)=O)=C(C=C1)F
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Maryanoff BE, et al. Discovery of potent peptide-mimetic antagonists for the human thrombin receptor, protease-activated receptor-1 (PAR-1). Curr Med Chem Cardiovasc Hematol Agents. 2003;1(1):13-36. [Content Brief]
[2]. Damiano BP, et al. RWJ-58259: a selective antagonist of protease activated receptor-1. Cardiovasc Drug Rev. 2003;21(4):313-326. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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