Home GPCR & G Protein PAR antagonist Vorapaxar (MK-5348) For research use only.

Vorapaxar (MK-5348)

Synonyms: SCH 530348

Vorapaxar (SCH 530348, MK-5348) is a potent and orally active thrombin receptor (PAR-1) antagonist with Ki of 8.1 nM.

Vorapaxar (MK-5348) Chemical Structure

Vorapaxar (MK-5348) Chemical Structure

CAS No. 618385-01-6

Purity & Quality Control

Vorapaxar (MK-5348) Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 Function assay 15 mins Antagonist activity at human PAR1 expressed in HEK293 cells co-expressing Galpha15 assessed as inhibition of haTRAP-induced calcium mobilization preincubated for 15 mins followed by haTRAP addition by calcium-4 dye based FLIPR assay, IC50 = 0.064 μM. 28745507
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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
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]
Kinase Assay 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot AKT / JNK / NF-κB / GAPDH ATM / ATR / GSK / Cyclin D1 / GAPDH fibronectin / tubulin 31059055
Immunofluorescence proinflammatory signaling PLP / Olig2 25587041
In Vivo
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]
Animal Research Animal Models cynomolgus monkeys
Dosages 0.5, 0.3, 0.1, and 0.05 mg/kg
Administration oral

Chemical Information & Solubility

Molecular Weight 492.58 Formula

C29H33FN2O4
CAS No. 618385-01-6 SDF Download Vorapaxar (MK-5348) SDF
Smiles CCOC(=O)NC1CCC2C(C1)CC3C(C2C=CC4=NC=C(C=C4)C5=CC(=CC=C5)F)C(OC3=O)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 99 mg/mL ( (200.98 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 99 mg/mL

Water : Insoluble


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In vivo
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