Home Proteases HCV Protease inhibitor Grazoprevir For research use only.

Grazoprevir

Synonyms: MK5172

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 Chemical Structure

Grazoprevir Chemical Structure

CAS No. 1350514-68-9

Purity & Quality Control

Grazoprevir Related Products

Signaling Pathway

HCV Protease Signaling Pathways

HCV Protease Signaling Pathway

Cell Data

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
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Targets
gt1b [1]
(Cell-free assay)		 gt1a [1]
(Cell-free assay)		 gt1b R155K [1]
(Cell-free assay)		 gt2a [1]
(Cell-free assay)		 gt1b D168V [1]
(Cell-free assay)		 Click to View More Targets
0.01 nM(Ki) 0.01 nM(Ki) 0.07 nM(Ki) 0.08 nM(Ki) 0.14 nM(Ki)
In vitro
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].
Cell Research Cell lines HB1 cells
Concentrations 2, 5, or 10 nM
Incubation Time 1, 2, 3.5 days
Method 30,000 HB1 cells are seeded per well of a 6-well tissue culture plate per drug concentration. The next day (day 0), the medium is replenished with fresh medium and MK-5172 at the appropriate drug concentration. Cells from a single well per drug concentration are harvested on days 0, 1, and 2, washed, and stored frozen until evaluation. The fourth well is similarly harvested on day 3.5 except that 30,000 cells are reseeded with fresh medium and MK-5172 at the appropriate drug concentration. For additional time points, cells are passaged and harvested every one-half week for 2 weeks. For the third week, cells are similarly treated except that cells received replenishing medium which contained 0.5 mg/ml G418 without protease inhibitor.
In Vivo
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].
Animal Research Animal Models rats or dogs
Dosages 2 mg/kg of body weight (rat) or 0.5 mg/kg (dog)
Administration i.v.
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

Chemical Information & Solubility

Molecular Weight 766.9 Formula

C38H50N6O9S
CAS No. 1350514-68-9 SDF Download Grazoprevir SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (130.39 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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