PAR-1 ( Ki = 8.1 nM )
Vorapaxar sulfate (SCH 530348 sulfate) exhibits a strong IC50 of 47 nM for thrombin-induced platelet aggregation and a 25 nM IC50 for haTRAP-induced platelet aggregation. With a Ki of 1.1 nM, vorapaxar sulfate (SCH 530348 sulfate) inhibits the thrombin-induced calcium transient in human coronary artery smooth muscle cells (HCASMC). Additionally, with a Ki of 13 nM, it prevents thrombin-stimulated thymidine incorporation in HCASMC[1].

Vorapaxar sulfate (SCH 530348 sulfate) exhibits a strong IC50 of 47 nM for thrombin-induced platelet aggregation and a 25 nM IC50 for haTRAP-induced platelet aggregation. With a Ki of 1.1 nM, vorapaxar sulfate (SCH 530348 sulfate) inhibits the thrombin-induced calcium transient in human coronary artery smooth muscle cells (HCASMC). Additionally, with a Ki of 13 nM, it prevents thrombin-stimulated thymidine incorporation in HCASMC[1].

The most serious side effect of the PAR1 antagonist vorapaxar is an increased incidence of intracranial hemorrhage, primarily occurring in patients with a history of stroke. In patients without a history of stroke, the increased incidence of intracranial hemorrhage is less than 1 case per 1000 treatment years. [1]

[1]. PAR1 contributes to influenza A virus pathogenicity in mice. J Clin Invest. 2013 Jan;123(1):206-14.

[2]. Vorapaxar: A novel agent to be considered in the secondary prevention of myocardial infarction. J Pharm Bioallied Sci. 2016 Apr-Jun;8(2):98-105.

Vorapaxar sulfate is an organic sulfate prepared by reacting vorapazol with an equimolar amount of sulfuric acid. It is a protease-activated receptor-1 (PAR-1) antagonist used to reduce the incidence of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral artery disease. Studies have shown that it reduces the composite endpoint of cardiovascular death, myocardial infarction, stroke, and emergency coronary revascularization. It has multiple effects, including cardiovascular action, platelet aggregation inhibition, and PAR-1 antagonism. It contains a vorapazol (1+) molecule. Vorapaxar sulfate is the sulfate form of vorapazol, a highly bioavailable orally bioavailable PAR-1 antagonist with antiplatelet activity. After oral administration, vorapazol binds to PAR-1 expressed on platelets, inhibiting PAR-1-mediated platelet aggregation. Vorapaxar inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation, but does not inhibit adenosine diphosphate (ADP), collagen, or thromboxane analogue-induced platelet aggregation. See also: Vorapaxar (with active moiety). Indications for use: Zontivity is indicated for reducing the risk of atherosclerotic thrombotic events in adult patients with a history of myocardial infarction (MI) in combination with acetylsalicylic acid (ASA) and, where appropriate, clopidogrel; or for symptomatic peripheral artery disease (PAD) in combination with acetylsalicylic acid (ASA) or, as appropriate, clopidogrel. PAR1 antagonist Vorapaxar has been studied as a potential antithrombotic agent in approximately 40,000 patients over a 3-year period. [1] Short-term PAR1 antagonism appears to be relatively safe. Given the protective effect of the PAR1 antagonist (using SCH79797) against influenza A virus (IAV) infection in mice in this study, it is recommended that Vorapaxar or similar PAR1 antagonists be explored for the treatment of IAV in other preclinical models, and that human studies be conducted where appropriate. [1] Since H1N1 and H3N2 subtypes of influenza virus are currently circulating in the human population, it is reasonable to infer that PAR1 antagonists like Vorapaxar are likely also effective against seasonal influenza viruses. [1]

C29H35FN2O8S

590.6602

590.209

C, 58.97; H, 5.97; F, 3.22; N, 4.74; O, 21.67; S, 5.43

705260-08-8

Vorapaxar; 618385-01-6

10077129

White to off-white solid powder

6.261

3

10

6

41

902

7

CCOC(N[C@@H]1CC[C@@H]2[C@H](C[C@@H]3[C@H]([C@H]2/C=C/C4=NC=C(C5=CC(F)=CC=C5)C=C4)[C@H](OC3=O)C)C1)=O.OS(=O)(O)=O

NQRYCIGCIAWEIC-CKLVGUEFSA-N

InChI=1S/C29H33FN2O4.H2O4S/c1-3-35-29(34)32-23-10-11-24-20(14-23)15-26-27(17(2)36-28(26)33)25(24)12-9-22-8-7-19(16-31-22)18-5-4-6-21(30)13-18;1-5(2,3)4/h4-9,12-13,16-17,20,23-27H,3,10-11,14-15H2,1-2H3,(H,32,34);(H2,1,2,3,4)/b12-9+;/t17-,20+,23-,24-,25+,26-,27+;/m1./s1

ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate;sulfuric acid

SCH-530348; Zontivity; SCH530348; SCH 530348; Vorapaxar sulfate; Vorapaxar

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 25~99 mg/mL (50.8~201 mM)
Ethanol: ~99 mg/mL

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 1.67mg/ml (3.39mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)