Grazoprevir

SKU: orb1302768

Description

Grazoprevir is a macrocyclic protease inhibitor targeting the HCV NS3/4A protein. It is utilized in research, notably in combination with elbasvir, to study antiviral mechanisms and efficacy in both in vitro assays and in vivo models of hepatitis C virus infection.

Research Area

Infectious Disease & Virology, Protein Biochemistry

Key Properties

• CAS Number: 1350514-68-9
• MW: 766.9
• Purity: 99.99%
• Formula: C₃₈H₅₀N₆O₉S
• SMILES: [H][C@@]12C[C@@]1([H])OC(=O)N[C@]([H])(C(=O)N1C[C@@]([H])(C[C@H]1C(=O)N[C@@]1(C[C@H]1C=C)C(=O)NS(=O)(=O)C1CC1)Oc1nc3cc(OC)ccc3nc1CCCCC2)C(C)(C)C
• Target: SARS-CoV,HCV Protease
• Solubility: DMSO:125 mg/mL (162.99 mM);Ethanol:15 mg/mL (19.56 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (2.61 mM)

Bioactivity

• Target IC50:
  GT3a:0.90 nM (Ki)|GT2b:0.15 nM (Ki)|GT1b:0.01 nM (Ki)|GT2a:0.08 nM (Ki)|GT1a:0.01 nM (Ki)
• In Vivo:
  When dosed to dogs, Grazoprevir shows low clearance of 5 mL/min/kg and a 3 h half-life after iv dosing and has good plasma exposure (AUC: 0.4 μM/h) after a 1 mg/kg oral dose. Dog liver biopsy studies showed that the liver concentration of Grazoprevir after the 1 mg/kg oral dose is 1.4 μM at the 24 h time point. Similar to its behaviour in rats, Grazoprevir demonstrates effective partitioning into liver tissue and maintains high liver concentration, relative to potency, 24 h after oral dosing in dogs .
• In Vitro:
  In biochemical assays, Grazoprevir is effective against a panel of major genotypes and variants engineered with common resistant mutations, with Ki of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), 0.07 nM (gt1bR155K), 0.14 nM (gt1bD168V), 0.30 nM (gt1bD168Y), 5.3 nM (gt1bA156T), and 12 nM (gt1bA156V), respectively. In the replicon assay, Grazoprevir demonstrates subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a, with EC50s of 0.5±0.1 nM, 2±1 nM, and 2±1 nM for gt1bcon1, gt1a, and gt2a, respectively. Grazoprevir is potent against a panel of HCV replication mutants NS5A (Y93H) (EC50: 0.7 nM), NS5B nucleosides (S282T) (EC50: 0.3 nM), and NS5B (C316Y) (EC50: 0.4 nM). Grazoprevir maintains the excellent potency against the gt 3a enzyme as well as a broad panel of mutant enzymes, has excellent potency in the replicon system [gt1b IC50(50% NHS): 7.4 nM; gt1a IC50(40% NHS): 7 nM], and shows excellent rat liver exposure.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, MK5172, MK-5172, MK 5172, Inhibitor, HCV, HCV NS3/4A protease, HCVProtease, HCV Protease, Hepatitis C virus, gt1a, gt1b, Grazoprevir, SARS coronavirus, SARSCoV, SARS-CoV

Compound Identifiers

PubChem CID

44603531