Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C38H50N6O9S.H2O |
Molecular Weight | 784.919 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.[H][C@@]12C[C@@]1([H])OC(=O)N[C@H](C(=O)N3C[C@@]([H])(C[C@H]3C(=O)N[C@@]4(C[C@@]4([H])C=C)C(=O)NS(=O)(=O)C5CC5)OC6=NC7=CC(OC)=CC=C7N=C6CCCCC2)C(C)(C)C
InChI
InChIKey=RXSARIJMSJWJLZ-CIAYNJNFSA-N
InChI=1S/C38H50N6O9S.H2O/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);1H2/t21-,22-,24-,29+,30-,31-,38-;/m1./s1
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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0.02 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | ZEPATIER Approved UseZEPATIER 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 Date2016 |
PubMed
Title | Date | PubMed |
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Identification of the E5 open reading frame of human papillomavirus type 16. | 1988 Mar |
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Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. | 2012 Apr 12 |
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MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. | 2012 Aug |
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Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis. | 2017 |
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Elbasvir/grazoprevir. | 2017 Feb |
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Elbasvir/Grazoprevir (Zepatier) for Hepatitis C Virus Infection. | 2017 Mar 15 |
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Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4. | 2017 May |
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Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study. | 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 Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22615282
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.
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J05AP54
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ACTIVE MOIETY
SUBSTANCE RECORD