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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Asunaprevir (formerly BMS-650032; BMS-650032; trade name in Japan and Russia: Sunvepra) is a potent and orally bioavailable small molecule inhibitor of the hepatitis C virus (HCV) NS3 (non-structural) protease that has been approved for use in Japan as part of a combination treatment for HCV infections. It inhibits HCV NS3 protease with an IC50 of 0.2 nM-3.5 nM. HCV serine protease NS3 is required for protein processing during viral replication. Asunaprevir is an experimental drug candidate for the treatment of hepatitis C. It is being tested in combination with pegylated interferon and ribavirin, as well as in interferon-free regimens with other direct-acting antiviral agents including daclatasvir. It is currently in Phase III clinical trials.
| Targets |
HCV NS3 protease(IC50≈0.2 nM-3.5 nM)
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| ln Vitro |
Asunaprevir (ASV) inhibits the NS3 proteolytic activity of genotype 1a (H77 strain) and genotype 1b (J4L6S strain), with IC50s of 0.7 and 0.3 nM, respectively. The EC50s of ASV against replicons encoding the NS3 protease domains representing genotypes 1a, 1b, and 4a, range from 1.2 to 4.0 nM.
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| ln Vivo |
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| Enzyme Assay |
Asunaprevir (ASV) inhibits the NS3 proteolytic activity of genotype 1a (H77 strain) and genotype 1b (J4L6S strain), with IC50s of 0.7 and 0.3 nM, respectively. The EC50s of ASV against replicons encoding the NS3 protease domains representing genotypes 1a, 1b, and 4a, range from 1.2 to 4.0 nM.
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| Cell Assay |
Cytotoxicity is determined by incubating cells (3,000 to 10,000 cells/well) with serially diluted test compounds or DMSO for 5 days (MT-2 cells) or 4 days (all other cell types). Cell viability is quantitated using an MTS assay for MT-2 or a Cell-Titer Blue reagent assay for HEK-293, HuH-7, HepG2, and MRC5 cells, and 50% cytotoxic concentrations (CC50s) are calculated. For the HCV and BVDV replicon assays, CC50s are determined from the same wells that are later used to determine EC50s.
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| Animal Protocol |
Asunaprevir (ASV) is administered orally to mice (n = 9 per group; overnight fast; vehicle: PEG-400-ethanol, 9:1). Retro-orbital bleeding is used to obtain blood samples (-0.2 mL) at 0.25, 0.5, 1, 3, 6, 8, and 24 hours following dosing. To create a composite pharmacokinetic profile, three animals in each group are bled at 0.25, 3, and 24 hours, three at 0.5 and 6 hours, and three at 1 and 8 hours. At the terminal sampling points, mice are also deprived of their livers and brains.Amorphous free acid (ASV) is given orally to rats (n=3 per group; overnight fast) at doses of 3, 5, 10, and 15 mg/kg in PEG-400-ethanol (9:1). The jugular vein is used to draw serial blood samples (-0.3 mL) prior to dosing (0 h) and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 24, and 48 h after dosing. Rats are given ASV (5 or 15 mg/kg, same vehicle as above) orally in order to measure tissue exposure. Samples of the rats' liver, heart, and blood are taken at intervals of 0.17, 0.5, 1, 2, 4, 6, 8, 24, 48, and 72 hours following dosing.
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| References |
| Molecular Formula |
C35H46CLN5O9S
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| Molecular Weight |
748.29
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| Exact Mass |
747.27
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| Elemental Analysis |
C, 56.18; H, 6.20; Cl, 4.74; N, 9.36; O, 19.24; S, 4.28
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| CAS # |
630420-16-5
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
O=C(OC(C)(C)C)N[C@H](C(N1[C@H](C(N[C@@]2(C(NS(=O)(C3CC3)=O)=O)[C@H](C=C)C2)=O)C [C@@H](OC4=NC=C(OC)C5=C4C=C(Cl)C=C5)C1)=O)C(C)(C)C
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| InChi Key |
XRWSZZJLZRKHHD-WVWIJVSJSA-N
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| InChi Code |
InChI=1S/C35H46ClN5O9S/c1-9-19-16-35(19,31(44)40-51(46,47)22-11-12-22)39-28(42)25-15-21(49-29-24-14-20(36)10-13-23(24)26(48-8)17-37-29)18-41(25)30(43)27(33(2,3)4)38-32(45)50-34(5,6)7/h9-10,13-14,17,19,21-22,25,27H,1,11-12,15-16,18H2,2-8H3,(H,38,45)(H,39,42)(H,40,44)/t19-,21-,25+,27-,35-/m1/s1
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| Chemical Name |
1,1-dimethylethyl ((1S)-1-{((2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-2-({(1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-ethenylcyclopropyl}carbamoyl) pyrrolidin-1-yl)carbonyl}-2,2-dimethylpropyl)carbamate
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| Synonyms |
BMS-650032; BMS 650032; BMS650032; trade name in Japan and Russia: Sunvepra
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL ( ~133.63 mM )
Ethanol : 20~100 mg/mL(~26.73 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.34 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (3.34 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: 2 mg/mL (2.67 mM) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 6: ≥ 2 mg/mL (2.67 mM) (saturation unknown) in 10% EtOH + 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 20.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 7: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.34 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3364 mL | 6.6819 mL | 13.3638 mL | |
| 5 mM | 0.2673 mL | 1.3364 mL | 2.6728 mL | |
| 10 mM | 0.1336 mL | 0.6682 mL | 1.3364 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Asunaprevir activates ISRE activity and type I IFN and TLR3/RIG-I antiviral signaling pathway.Front Microbiol. 2017; 8: 668. |
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 Effects of Asunaprevir on TLR3/RIG-I signaling pathway in Huh. 7.5.1 cells with MAVS and TRIF knockdown. Huh 7.5.1 cells were transfected by siRNA of MAVS and TRIF for 48 h and then treated with asunaprevir for 24 h. The key signaling proteins such as MAVS, TRIF, IRF3, and phosphorylated IRF-3 were determined by immunoblotting analysis (left panel).Front Microbiol. 2017; 8: 668. |
Effects of Asunaprevir on replication of DENV and HCV. (A)Huh 7.5.1 cells were treated with different doses of asunaprevir for 24 h and immunoblotting analysis for NS3 protein of DENV, and real-time PCR for RNA level of DENV were performed(B).Front Microbiol. 2017; 8: 668. |
 Asunaprevir inhibits DENV-2 and HCV virus production.Front Microbiol. 2017; 8: 668. |
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Effects of asunaprevir on replication of HCV in JFH-1- infected.Front Microbiol. 2017; 8: 668. |
 Effects of asunaprevir on replication of DENV in Huh 7.5.1 cells after knockdown of MAVS and TRIF by siRNA.Front Microbiol. 2017; 8: 668. |
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