Home Proteases HCV Protease inhibitor Grazoprevir

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Grazoprevir HCV Protease inhibitor

Cat.No.S3728

Grazoprevir anhydrous (MK5172) is a Hepatitis C Virus NS3/4A Protease inhibitor with IC50 values of 7pM, 4pM, and 62pM for HCV genotype 1a, 1B, and 4 respectively.
Grazoprevir HCV Protease inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 766.9

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 1a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method, EC50=0.0003μM. 26819676
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 1b infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method, EC50=0.0003μM. 26819676
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 1a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method, EC50=0.0006μM. 27994759
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 1b infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method, EC50=0.0006μM. 27994759
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 2a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method, EC50=0.0012μM. 26819676
HuH7 Antiviral assay 72 hrs Antiviral activity against Hepatitis C virus genotype 1b infected in HuH7 cells assessed as reduction in replicon RNA level after 72 hrs by TaqMan-based RT-PCR analysis in presence of 10% FBS, EC50=0.0015μM. 24900818
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 2b infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method, EC50=0.005μM. 26819676
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 2a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method, EC50=0.0054μM. 27994759
HuH7 Antiviral assay 24 hrs Antiviral activity against Hepatitis C virus genotype 1a infected in human HuH7 cells assessed as inhibition of viral replication after 24 hrs presence of 40% NHS, IC50=0.007μM. 24900473
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 3a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method, EC50=0.0072μM. 26819676
HuH7 Antiviral assay 72 hrs Antiviral activity against HCV genotype 3a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method, EC50=0.0072μM. 27994759
HuH7 Antiviral assay 24 hrs Antiviral activity against Hepatitis C virus (isolate Con1) genotype 1b infected in human HuH7 cells assessed as inhibition of viral replication after 24 hrs in presence of 50% NHS, IC50=0.0074μM. 24900473
HuH7 Antiviral assay 72 hrs Antiviral activity against Hepatitis C virus genotype 3a infected in HuH7 cells assessed as reduction in replicon RNA level after 72 hrs by TaqMan-based RT-PCR analysis in presence of 10% FBS, EC50=0.013μM. 24900818
HBI10A Antiviral assay Antiviral activity against Hepatitis C virus subtype 1b infected in HBI10A cells harboring HCV subgenomic bicistronic replicon assessed as reduction in viral replication, EC50=0.002μM. ChEMBL
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Chemical Information, Storage & Stability

Molecular Weight 766.9 Formula

C38H50N6O9S

 Storage (From the date of receipt)
CAS No. 1350514-68-9 Download SDF Storage of Stock Solutions

Synonyms MK5172 Smiles CC(C)(C)C1C(=O)N2CC(CC2C(=O)NC3(CC3C=C)C(=O)NS(=O)(=O)C4CC4)OC5=NC6=C(C=CC(=C6)OC)N=C5CCCCCC7CC7OC(=O)N1

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (130.39 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

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% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
gt1b [1]
(Cell-free assay)
0.01 nM(Ki)
gt1a [1]
(Cell-free assay)
0.01 nM(Ki)
gt1b R155K [1]
(Cell-free assay)
0.07 nM(Ki)
gt2a [1]
(Cell-free assay)
0.08 nM(Ki)
gt1b D168V [1]
(Cell-free assay)
0.14 nM(Ki)
gt2b [1]
(Cell-free assay)
0.15 nM(Ki)
gt1b D168Y [1]
(Cell-free assay)
0.3 nM(Ki)
gt3a [1]
(Cell-free assay)
0.9 nM(Ki)
In vitro
MK-5172 is a novel P2-P4 quinoxaline macrocyclic NS3/4a protease inhibitor currently in clinical development. The compound demonstrates subnanomolar activity against a broad enzyme panel encompassing major hepatitis C virus (HCV) genotypes as well as variants resistant to earlier protease inhibitors[1].
In vivo
In both rat and dog, MK-5172 demonstrates good plasma and liver exposures, with 24-h liver levels suggestive of once-daily dosing. When administered to HCV-infected chimpanzees harboring chronic gt1a or gt1b infections, MK-5172 suppresses viral load between 4 to 5 logs at a dose of 1 mg/kg of body weight twice daily (b.i.d.) for 7 days. MK-5172 demonstrates low to moderate clearance and a modest half-life in both rat and dog. Upon oral administration, MK-5172 demonstrates modest bioavailability of 12 to 13%, with moderate plasma exposure in both species. Significant liver concentrations are achieved in both rat and dog. The 24-h trough liver concentrations are 0.2 μM in rat and 1.4 μM in dog (1 mg per kg), yielding exposure multiples of 27- to 200-fold over the serum-adjusted replicon EC50. MK-5172 proves highly efficacious in vivo at moderate doses against chronic-HCV-infected chimpanzees, including greater viral load suppression than vaniprevir when dosed alternatively to the same animal at an otherwise identical dose and frequency[1].
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03105349 Withdrawn
HCV
Fundacion SEIMC-GESIDA
 July 1 2017 Phase 4
NCT03145623 Completed
Hepatitis C|Chronic Kidney Diseases
University Hospital Toulouse|MSD France
 June 2 2017 --
NCT02973503 Completed
Chronic HCV Infection
University Hospital Clermont-Ferrand|Merck Sharp & Dohme LLC
 January 11 2017 Phase 3

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