Vorapaxar sulfate, the sulfuric acid salt form of Vorapaxar (also known as SCH-530348; Zontivity), is an orally bioactive anti-platelet drug acting as a thrombin receptor protease-activated receptor (PAR-1) antagonist. In 2014, the FDA approved Vorapaxar to help people with poor blood flow or heart attacks avoid having heart attacks and strokes.
Physicochemical Properties
| Molecular Formula | C29H35FN2O8S |
| Molecular Weight | 590.6602 |
| Exact Mass | 590.209 |
| Elemental Analysis | C, 58.97; H, 5.97; F, 3.22; N, 4.74; O, 21.67; S, 5.43 |
| CAS # | 705260-08-8 |
| Related CAS # | Vorapaxar; 618385-01-6 |
| PubChem CID | 10077129 |
| Appearance | White to off-white solid powder |
| LogP | 6.261 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 41 |
| Complexity | 902 |
| Defined Atom Stereocenter Count | 7 |
| SMILES | 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 |
| InChi Key | NQRYCIGCIAWEIC-CKLVGUEFSA-N |
| InChi Code | 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 |
| Chemical Name | 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 |
| Synonyms | SCH-530348; Zontivity; SCH530348; SCH 530348; Vorapaxar sulfate; Vorapaxar |
| HS Tariff Code | 2934.99.9001 |
| Storage |
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. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PAR-1 ( Ki = 8.1 nM ) |
| ln Vitro | 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]. |
| References |
[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. |
| Additional Infomation |
Vorapaxar sulfate is an organic sulfate salt obtained by combining vorapaxar with one molar equivalent of sulfuric acid. A protease-activated receptor-1 antagonist used for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation. It has a role as a cardiovascular drug, a platelet aggregation inhibitor and a protease-activated receptor-1 antagonist. It contains a vorapaxar(1+). Vorapaxar Sulfate is the sulfate salt form of vorapaxar, an orally bioavailable protease-activated receptor-1 (PAR-1) antagonist, with antiplatelet activity. Upon oral administration, vorapaxar binds to PAR-1 expressed on platelets, and inhibits PAR-1-mediated platelet aggregation. Vorapaxar inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation, and does not inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or a thromboxane mimetic. See also: Vorapaxar (has active moiety). Drug Indication Zontivityis indicated for the reduction of atherothrombotic events in adult patients with- a history of myocardial infarction (MI), ,co-administered with acetylsalicylic acid (ASA) and, where appropriate, clopidogrel; or- symptomatic peripheral arterial disease(PAD), co-administered with acetylsalicylic acid (ASA) or, where appropriate, clopidogrel. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 25~99 mg/mL (50.8~201 mM) Ethanol: ~99 mg/mL |
| Solubility (In Vivo) |
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. 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. Solubility in Formulation 3: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 1.67mg/ml (3.39mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6930 mL | 8.4651 mL | 16.9302 mL | |
| 5 mM | 0.3386 mL | 1.6930 mL | 3.3860 mL | |
| 10 mM | 0.1693 mL | 0.8465 mL | 1.6930 mL |