Vorapaxar (MK-5348)

Catalog No.S8067 Batch:S806702

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Technical Data

Formula

C29H33FN2O4

Molecular Weight 492.58 CAS No. 618385-01-6
Solubility (25°C)* In vitro DMSO 99 mg/mL (200.98 mM)
Ethanol 99 mg/mL (200.98 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Vorapaxar (SCH 530348, MK-5348) is a potent and orally active thrombin receptor (PAR-1) antagonist with Ki of 8.1 nM.
Targets
PAR-1 [1]
(Cell-free assay)
8.1 nM(Ki)
In vitro

SCH 530348 is a synthetic tricyclic 3-phenylpyridine and an orally active himbacine-based thrombin-receptor antagonist. SCH 530348 shows potent inhibition of thrombin-induced platelet aggregation with an IC50 of 47 nM and haTRAP-induced platelet aggregation with an IC50 of 25 nM, whereas it shows no inhibition of platelet aggregation induced by other agonists such as ADP, collagen and a PAR-4 agonist peptide. SCH 530348 also has no affect on the prothrombin time (PT), partial thromboplastin time (PTT), or activated partial thromboplastin time (aPTT). Moreover, SCH 530348 causes no increase in the bleeding time or in surgical bleeding compared with inactive control. SCH530348 is found to be selective for PAR-1 when tested over a number of ion channels and receptors, including PAR-4 receptor. [1]

In vivo

SCH 530348 is well absorbed in rat (68%; 10 mg/kg) and in monkey (82%; 1 mg/kg) models. Tmax is observed at about 3 h in rats and 1 h in monkeys. The elimination half-life is 5.1 h in rats and 13 h in monkeys. The oral bioavailability is 33% in rats and 86% in monkeys. In preclinical studies in cynomolgus monkey platelets, oral administration of SCH 530348 at a dose greater than 0.1 mg/kg resulted in 100% inhibition of thrombin-receptor agonist peptide (TRAP)-induced platelet aggregation for 24 h with partial recovery occurring at 48 h. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • In vitro PAR-1 binding assay

    Human platelet membranes (700 mg) are prepared from 40 units of fresh human platelets. Thrombin receptor antagonists are screened using a modification of the thrombin receptor radioligand binding assay Human platelet membranes (40μg) are incubated with 10nM of [3H]haTRAP (alanine-p-fluorophenylalaninearganine-cyclohexylalanine-homoarganine-[ 3H]phenylalanine amide) in the presence of compounds at concentrations of 1 nM, 3 nM, 30 nM, 100 nM, 300 nM and 1μM (5% DMSO final concentration) in binding buffer (50 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.1% BSA). The plates are covered and vortex-mixed gently on a plate shaker for 1 h at room temperature. The incubated membranes are harvested using a Packard FilterMate Universal Harvester onto Packard UniFilter GF/C filter plates which are soaked for at least 1 hour in 0.1% polyethyleneimine and then rapidlywashed four times with 300 μL ice cold binding buffer without BSA. MicroScint 20 scintillation cocktail is added to each well, and the plates are counted in a Packard TopCount Microplate Scintillation Counter. The specific binding is defined as the total binding minus the nonspecific binding observed in the presence of excess (50 μM) unlabeled haTRAP.

Animal Study:

[1]

  • Animal Models

    cynomolgus monkeys

  • Dosages

    0.5, 0.3, 0.1, and 0.05 mg/kg

  • Administration

    oral

Selleck's Vorapaxar (MK-5348) has been cited by 16 publications

Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma [ J Immunother Cancer, 2024, 12(11)e009805] PubMed: 39581704
Protease activated receptor-1 regulates mixed lineage kinase-3 to drive triple-negative breast cancer tumorigenesis [ Cancer Lett, 2024, 603:217200] PubMed: 39222677
Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease [ Acta Pharm Sin B, 2023, 13(2):662-677] PubMed: 36873178
Rivaroxaban attenuates neutrophil maturation in the bone marrow niche [ Basic Res Cardiol, 2023, 118(1):31] PubMed: 37580509
The Effect of 4-Methylcatechol on Platelets in Familial Hypercholesterolemic Patients Treated with Lipid Apheresis and/or Proprotein Convertase Subtilisin Kexin 9 Monoclonal Antibodies [ Nutrients, 2023, 15(8)1842] PubMed: 37111061
Porovnanie agregácie doštičiek u zdravých dobrovoľníkov [ Charles University Digital Repository, 2023, ] PubMed: none
The Antiplatelet Effect of 4-Methylcatechol in a Real Population Sample and Determination of the Mechanism of Action [ Nutrients, 2022, 14(22)4798] PubMed: 36432485
Comparison of Antiplatelet Effects of Phenol Derivatives in Humans [ Biomolecules, 2022, 12(1)117] PubMed: 35053265
Probing the signaling requirements for naive human pluripotency by high-throughput chemical screening [ Cell Rep, 2021, 35(11):109233] PubMed: 34133938
Pleiotropic Effects of the Protease-Activated Receptor 1 (PAR1) Inhibitor, Vorapaxar, on Atherosclerosis and Vascular Inflammation [ Cells, 2021, 10(12)3517] PubMed: 34944024

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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