Asunaprevir

SKU: orb1302828

Description

Asunaprevir (BMS-650032) is a small molecule inhibitor targeting the hepatitis C virus NS3 protease. It has been utilized in research for both in vitro enzymatic assays and in vivo animal studies to investigate antiviral mechanisms and combination therapies against HCV infection.

Research Area

Molecular Biology, Protein Biochemistry

Key Properties

• CAS Number: 630420-16-5
• MW: 748.3
• Purity: >98%
• Formula: C₃₅H₄₆ClN₅O₉S
• SMILES: COc1cnc(O[C@H]2C[C@H](N(C2)C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)C(=O)N[C@@]2(C[C@H]2C=C)C(=O)NS(=O)(=O)C2CC2)c2cc(Cl)ccc12
• Target: Protease
• Solubility: Soluble in DMSO (up to at least 50 mg/ml)

Bioactivity

• Target IC50:
  HCV 1a H77:0.7 nM|5a (SA13):1.7 nM|1b J4L6S:0.3 nM|6a (HK-6A):0.9 nM|4a (ED43):1.6 nM
• In Vivo:
  Asunaprevir, administered orally at doses ranging from 3-15 mg/kg, exhibits a hepatotropic disposition, evidenced by liver-to-plasma ratios spanning from 40 to 359 across different animal species. Twenty-four hours after administration, liver exposure levels in all evaluated species were at least 110 times greater than the inhibitor EC50 noted against HCV genotype-1 replicons.
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• In Vitro:
  Asunaprevir 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. Replicon cells are maintained under selective pressure with asunaprevir at concentrations of 10 and 30 times the EC50 values (50 or 150 nM final concentrations, respectively). For genotype 1b resistance selection, replicon cells are maintained in the presence of asunaprevir at 10 or 30 times the EC50 values (30 or 90 nM final concentrations, respectively). Asunaprevir, administered at single or multiple doses of 200 to 600 mg twice daily, is generally well tolerated, achieving rapid and substantial decreases in HCV RNA levels in subjects chronically infected with genotype 1 HCV.
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• Cell Research:
  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.
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• Animal Research:
  Mice (n=9 per group; overnight fast) receive Asunaprevir (ASV) by oral gavage (5 mg/kg; a vehicle of PEG-400-ethanol, 9:1). Blood samples (-0.2 mL) are obtained by retro-orbital bleeding at 0.25, 0.5, 1, 3, 6, 8, and 24 h after dosing. Within each group, three animals are bled at 0.25, 3, and 24 h, three at 0.5 and 6 h, and three at 1 and 8 h, resulting in a composite pharmacokinetic profile. Livers and brains are also removed from mice at the terminal sampling points. Rats (n=3 per group; overnight fast) receive ASV (amorphous free acid) by oral gavage (3, 5, 10, and 15 mg/kg) in PEG-400-ethanol (9:1). Serial blood samples (-0.3 mL) are obtained from the jugular vein predosing (0 h) and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 24, and 48 h post dosing. To assess tissue exposure, rats are orally administered ASV (5 or 15 mg/kg, same vehicle as above), and blood, liver, and heart samples from two rats/group are obtained at 0.17, 0.5, 1, 2, 4, 6, 8, 24, 48, and 72 h after dosing.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BMS-650032

Compound Identifiers

PubChem CID

124250787