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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

Estructura química

Peso molecular: 766.9

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.99%
99.99

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad 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
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 766.9 Fórmula

C38H50N6O9S

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 1350514-68-9 Descargar SDF Almacenamiento de soluciones madre

Sinónimos 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

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (130.39 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 100 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa Concentración Volumen Peso molecular
Calculadora de Dilución Calculadora de Peso Molecular

In vivo
Lote:

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

mg/kg g μL

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH2O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (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.
Referencias

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT Reclutamiento Condiciones Patrocinador/Colaboradores Fecha de inicio Fases
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