U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H50N6O9S
Molecular Weight 766.903
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GRAZOPREVIR ANHYDROUS

SMILES

COC1=CC2=NC3=C(CCCCC[C@@H]4C[C@H]4OC(=O)N[C@H](C(=O)N5C[C@@H](C[C@H]5C(=O)N[C@@]6(C[C@H]6C=C)C(=O)NS(=O)(=O)C7CC7)O3)C(C)(C)C)N=C2C=C1

InChI

InChIKey=OBMNJSNZOWALQB-NCQNOWPTSA-N
InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1

HIDE SMILES / InChI

Molecular Formula C38H50N6O9S
Molecular Weight 766.903
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Grazoprevir is a second generation NS3/4A protease inhibitor approved in the EU and the USA for the treatment of hepatitis C virus (HCV) genotypes 1 and 4 infections in adult patients in combination with elbasvir (C virus (HCV) NS5A inhibitor) as the fixed-dose combination product Zepatier with or without ribavirin. In phase III trials, 12 or 16 weeks of treatment with once-daily elbasvir/grazoprevir (fixed-dose tablet or as individual agents), taken with or without ribavirin, generally provided high rates of sustained virological response at 12 weeks (SVR12) in treatment-naive and -experienced adult patients with chronic HCV genotype 1a, 1b or 4 infection, including those with or without compensated cirrhosis, HIV co-infection, inherited blood disorders or chronic kidney disease or patients receiving opioid agonist therapy or of Japanese origin. Elbasvir/grazoprevir was generally well tolerated. Thus, elbasvir/grazoprevir, with or without ribavirin, represents an effective new option for the treatment of adults with chronic HCV genotype 1 and 4 infection, including a number of difficult-to-treat populations.

Originator

Curator's Comment: # Merck

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZEPATIER

Approved Use

ZEPATIER is a fixed-dose combination product containing elbasvir, a hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated for treatment of chronic HCV genotype 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin in certain patient populations.

Launch Date

2016
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
165 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GRAZOPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1420 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GRAZOPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
31 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GRAZOPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.2%
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GRAZOPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor.
2012 Apr 12
MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants.
2012 Aug
Elbasvir/Grazoprevir (Zepatier) for Hepatitis C Virus Infection.
2017 Mar 15
Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4.
2017 May
Elbasvir/grazoprevir does not worsen renal function in patients with hepatitis C virus infection and pre-existing renal disease.
2017 Nov
Elbasvir/Grazoprevir Use in Postliver Transplantation Patients on Hemodialysis.
2017 Sep
Patents

Sample Use Guides

ZEPATIER is a two-drug, fixed-dose combination product containing 50 mg of elbasvir and 100 mg of grazoprevir in a single tablet. The recommended dosage of ZEPATIER is one tablet taken orally once daily with or without food
Route of Administration: Oral
In a cell-based replicon system, MK-5172 (Grazoprevir) inhibited HCV with EC50 values of 2 nM against genotype 1a, 0.5 nM against genotype 1b, 8 nM against genotype 2a and 13 nM against genotype 3. Also, MK-5172 is effective against HCV genotypes 1a, 2a, 1b, 2b and 3a.
Substance Class Chemical
Created
by admin
on Mon Mar 31 22:15:10 GMT 2025
Edited
by admin
on Mon Mar 31 22:15:10 GMT 2025
Record UNII
8YE81R1X1J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MK-5172
Preferred Name English
GRAZOPREVIR ANHYDROUS
Common Name English
CYCLOPROPANECARBOXAMIDE, N-((((1R,2R)-2-(5-(3-HYDROXY-6-METHOXY-2-QUINOXALINYL)PENTYL)CYCLOPROPYL)OXY)CARBONYL)-3-METHYL-L-VALYL-(4R)-4-HYDROXY-L-PROLYL-1-AMINO-N-(CYCLOPROPYLSULFONYL)-2-ETHENYL-, CYCLIC (1->2)-ETHER, (1R,2S)-
Systematic Name English
MK-5172 ANHYDROUS
Code English
Grazoprevir [WHO-DD]
Common Name English
grazoprevir [INN]
Common Name English
GRAZOPREVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000182639
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
Code System Code Type Description
SMS_ID
100000160903
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
CAS
1350514-68-9
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
NDF-RT
N0000190114
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
INN
9857
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
MERCK INDEX
m11947
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
FDA UNII
8YE81R1X1J
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
EVMPD
SUB174126
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
CAS
1206524-75-5
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
SUPERSEDED
NCI_THESAURUS
C175724
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
RXCUI
1871173
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
CAS
1356446-42-8
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
SUPERSEDED
EPA CompTox
DTXSID50159234
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
NDF-RT
N0000182638
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
PUBCHEM
44603531
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
DAILYMED
8YE81R1X1J
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY
NDF-RT
N0000190113
Created by admin on Mon Mar 31 22:15:10 GMT 2025 , Edited by admin on Mon Mar 31 22:15:10 GMT 2025
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
Related Record Type Details
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
IC50
SOLVATE->ANHYDROUS
TRANSPORTER -> SUBSTRATE
IC50
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION