General
Preferred name
GRAZOPREVIR
Synonyms
MK-5172 (sodium salt) ()
Grazoprevir sodium salt ()
MK-5172 ()
GRAZOPREVIR ANHYDROUS ()
Grazoprevir potassium salt ()
Grazoprevir hydrate ()
MK-5172 (potassium salt) ()
MK-5172 (hydrate) ()
MK5172 ()
MK-5172 sodium salt ()
MK-5172 potassium salt ()
Grazoprevir monohydrate ()
MK-5172 MONOHYDRATE ()
MK-5172 ANHYDROUS ()
P&D ID
PD016328
CAS
1350514-68-9
1206524-86-8
1350462-55-3
1425038-27-2
Tags
drug candidate
natural product
drug
available
Approved by
FDA
First approval
2016
Drug Status
investigational
approved
Max Phase
Phase 4
Phase 3
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
METABOLISM
Grazoprevir is partially eliminated by oxidative metabolism meditated by CYP3A [FDA Label]. No circulating metabolites of have been detected in human plasma.;
DESCRIPTION
Grazoprevir (MK-5172) is an HCV NS3/4A protease inhibitor class antiviral drug . In vitro evidence of activity against SARS-CoV-2 helicase and papain-like protease (PLpro) .
(GtoPdb)
DESCRIPTION
In biochemical assays, MK-5172 was effective against a panel of major genotypes and variants engineered with common resistant mutations observed in clinical studies with other NS3/4a protease inhibitors. In the replicon assay, MK-5172 demonstrated subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a.
In rats, MK-5172 showed a plasma clearance of 28 ml/min/kg and plasma half-life of 1.4 hr. When dosed p.o. at 5 mg/kg, the plasma exposure of MK-5172 was good with an AUC of 0.7 uM.hr. The liver exposure of the compound was quite good (23 uM at 4 hr), and MK-5172 remained in liver 24 hr after a single p.o. 5 mg/kg dose. At 24 hr, the liver concentration of MK-5172 was 0.2 uM, which was over 25-fold higher than the IC50 in the replicon assay with 50% NHS. When dosed to dogs, MK-5172 showed low clearance of 5 ml/min/kg and a 3 hr half-life after i.v. 2 mg/kg dosing and had good plasma exposure (AUC=0.4 uM.hr) after a p.o. 1 mg/kg dose. (BOC Sciences Bioactive Compounds)
In rats, MK-5172 showed a plasma clearance of 28 ml/min/kg and plasma half-life of 1.4 hr. When dosed p.o. at 5 mg/kg, the plasma exposure of MK-5172 was good with an AUC of 0.7 uM.hr. The liver exposure of the compound was quite good (23 uM at 4 hr), and MK-5172 remained in liver 24 hr after a single p.o. 5 mg/kg dose. At 24 hr, the liver concentration of MK-5172 was 0.2 uM, which was over 25-fold higher than the IC50 in the replicon assay with 50% NHS. When dosed to dogs, MK-5172 showed low clearance of 5 ml/min/kg and a 3 hr half-life after i.v. 2 mg/kg dosing and had good plasma exposure (AUC=0.4 uM.hr) after a p.o. 1 mg/kg dose. (BOC Sciences Bioactive Compounds)
DESCRIPTION
In biochemical assays, MK-5172 was effective against a panel of major genotypes and variants engineered with common resistant mutations observed in clinical studies with other NS3/4a protease inhibitors. In the replicon assay, MK-5172 demonstrated subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a.
In rats, MK-5172 showed a plasma clearance of 28 ml/min/kg and plasma half-life of 1.4 hr. When dosed p.o. at 5 mg/kg, the plasma exposure of MK-5172 was good with an AUC of 0.7 uM.hr. The liver exposure of the compound was quite good (23 uM at 4 hr), and MK-5172 remained in liver 24 hr after a single p.o. 5 mg/kg dose. At 24 hr, the liver concentration of MK-5172 was 0.2 uM, which was over 25-fold higher than the IC50 in the replicon assay with 50% NHS. When dosed to dogs, MK-5172 showed low clearance of 5 ml/min/kg and a 3 hr half-life after i.v. 2 mg/kg dosing and had good plasma exposure (AUC=0.4 uM.hr) after a p.o. 1 mg/kg dose. (BOC Sciences Bioactive Compounds)
In rats, MK-5172 showed a plasma clearance of 28 ml/min/kg and plasma half-life of 1.4 hr. When dosed p.o. at 5 mg/kg, the plasma exposure of MK-5172 was good with an AUC of 0.7 uM.hr. The liver exposure of the compound was quite good (23 uM at 4 hr), and MK-5172 remained in liver 24 hr after a single p.o. 5 mg/kg dose. At 24 hr, the liver concentration of MK-5172 was 0.2 uM, which was over 25-fold higher than the IC50 in the replicon assay with 50% NHS. When dosed to dogs, MK-5172 showed low clearance of 5 ml/min/kg and a 3 hr half-life after i.v. 2 mg/kg dosing and had good plasma exposure (AUC=0.4 uM.hr) after a p.o. 1 mg/kg dose. (BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
16
AdooQ Bioactive Compound Library
BOC Sciences Bioactive Compounds
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
NCATS Inxight Approved Drugs
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
49
Molecular Weight
766.34
Hydrogen Bond Acceptors
11
Hydrogen Bond Donors
3
Rotatable Bonds
7
Ring Count
7
Aromatic Ring Count
2
cLogP
3.3
TPSA
195.22
Fraction CSP3
0.63
Chiral centers
8.0
Largest ring
18.0
QED
0.35
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
HCV Protease
HCV
NS3/4a protease
GT1a
GT1b
SARS-CoV
Pathway
Metabolic Enzyme/Protease
Anti-infection
Immunology/Inflammation
Microbiology&virology
Proteases/Proteasome
MOA
Antiviral inhibitor
HCV inhibitor
Indication
hepatitis C
Solubility
In vitro:<br/>10 mM in DMSO
In Vitro:<br/>DMSO : ≥ 100 mg/mL(124.23 mM)<br/>In Vivo:<br/>1.Add each solvent one by one:10% DMSO >> 40%PEG300 >> 5%Tween-80 >> 45% saline<br/>Solubility: ≥ 2.5 mg/mL (3.11 mM)
Clear solution<br/>2.Add each solvent one by one:10% DMSO >> 90%corn oil<br/>Solubility: ≥ 2.5 mg/mL (3.11 mM)
Clear solution
Source data
