Home Proteases HCV Protease Inhibiteur Grazoprevir

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Grazoprevir HCV Protease Inhibiteur

Réf. Catalogue: S3728

Grazoprevir anhydre (MK5172) est un inhibiteur de la Hepatitis C Virus NS3/4A Protease avec des valeurs d'IC50 de 7pM, 4pM et 62pM pour les génotypes 1a, 1B et 4 du VHC respectivement.
Grazoprevir HCV Protease Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 766.9

Aller à

Contrôle Qualité (Quality Control)

Lot : Pureté : 99.99%
99.99

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires Type d'essai Concentration Temps d'incubation Formulation Description de l'activité 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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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire 766.9 Formule

C38H50N6O9S

 Stockage (À compter de la date de réception)
N° CAS 1350514-68-9 Télécharger le SDF Stockage des solutions mères

Synonymes 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

Solubilité (Solubility)

In vitro
Lot:

DMSO : 100 mg/mL (130.39 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 100 mg/mL

Water : Insoluble

Calculateur de molarité

Masse Concentration Volume Poids moléculaire
Calculateur de dilution Calculateur de poids moléculaire

In vivo
Lot:

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

mg/kg g μL

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH2O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Targets/IC50/Ki
gt1b
(Cell-free assay)
0.01 nM(Ki)
gt1a
(Cell-free assay)
0.01 nM(Ki)
gt1b R155K
(Cell-free assay)
0.07 nM(Ki)
gt2a
(Cell-free assay)
0.08 nM(Ki)
gt1b D168V
(Cell-free assay)
0.14 nM(Ki)
gt2b
(Cell-free assay)
0.15 nM(Ki)
gt1b D168Y
(Cell-free assay)
0.3 nM(Ki)
gt3a
(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.
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.
Références

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2025-07-15)

Numéro NCT Recrutement Conditions Promoteur/Collaborateurs Date de début Phases
NCT02940496 COMPLETED
BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma; Hepatitis C Infection; Refractory Liver Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7
M.D. Anderson Cancer Center
 2016-12-09 PHASE2
NCT03823911 COMPLETED
Cardiovascular Diseases; Hepatitis C; Hiv
University of Maryland, Baltimore
 2018-11-18 PHASE4
NCT02902120 COMPLETED
Hepatitis C; Renal Insufficiency, Chronic; Disorder of Transplanted Kidney
University of Maryland, Baltimore
 2017-05-01 PHASE4
NCT04546802 WITHDRAWN
Hepatocellular Carcinoma; Hepatoma; Liver Cell Carcinoma; Hepatitis C
Bayside Health
 2019-09 PHASE3
NCT03037151 UNKNOWN
Compensated Cirrhosis
The HIV Netherlands Australia Thailand Research Collaboration
 2018-08-01 PHASE4
NCT03026023 WITHDRAWN
Cardiac Transplant Disorder; Hepatitis C
Raymond T. Chung, MD
 2018-08-01 PHASE4