Identification
- Summary
Glecaprevir is a Hepatitis C NS3/4A protease inhibitor used to treat Hepatitis C.
- Brand Names
- Maviret, Mavyret
- Generic Name
- Glecaprevir
- DrugBank Accession Number
- DB13879
- Background
Glecaprevir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS3/4A protease inhibitor that targets the the viral RNA replication. In combination with Pibrentasvir, glecaprevir is a useful therapy for patients who experienced therapeutic failure from other NS3/4A protease inhibitors. It demonstrates a high genetic barrier against resistance mutations of the virus. In cell cultures, the emergence of amino acid substitutions at NS3 resistance-associated positions A156 or D/Q168 in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility to glecaprevir Label. The combinations of amino acid substitutions at NS3 position Y65H and D/Q168 also results in greater reductions in glecaprevir susceptibility, and NS3 Q80R in genotype 3a patients also leads to glecaprevir resistance Label.
Glecaprevir is available as an oral combination therapy with Pibrentasvir under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis 2. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both 2. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of ≥93% across genotypes 1a, 2a, 3a, 4, 5 and 6 Label.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Glecaprevir (DB13879)
- Weight
- Average: 838.87
Monoisotopic: 838.298310911 - Chemical Formula
- C38H46F4N6O9S
- Synonyms
- Glécaprévir
- Glecaprevir
- Glecaprevirum
- External IDs
- A-1282576
- A-1282576.0
- A-12825760
- ABT 493
- ABT-493
Pharmacology
- Indication
Indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both Label.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Pibrentasvir (DB13878) •••••••••••• •••••••• ••••••••• •••• •••••• •••••••• ••••••••• Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Pibrentasvir (DB13878) •••••••••••• •••••••• ••••••••• •••• •••• ••••••••• Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Pibrentasvir (DB13878) •••••••••••• •••••• Used in combination to treat Chronic hepatitis c virus (hcv) infection Combination Product in combination with: Pibrentasvir (DB13878) •••••••••••• •••••• ••••••••• •••• •••••• •• •• ••••• •• •• •••••••• •••••• Used in combination to treat Chronic hepatitis c genotype 2 Combination Product in combination with: Pibrentasvir (DB13878) •••••••••••• ••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In a biochemical assay studying clinical isolates of HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a, glecaprevir displayed IC50 values ranging from 3.5 to 11.3 nM that resulted in inhibition of the proteolytic activity of recombinant NS3/4A enzymes. In HCV replicon assays, glecaprevir had median EC50 values of 0.08-4.6 nM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a Label. In a QT study, glecaprevir is not shown to prolong the QTc interval.
- Mechanism of action
Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins Label. These multifunctional proteins, including NS3, are essential for viral replication. The N-terminal of NS3 protein confers serine protease activity, whileThe C-terminus of NS3 encodes a DExH/D-box RNA helicase which hydyolyzes NTP as an energy source to unwind double-stranded RNA in a 3′ to 5′ direction during replication of viral genomic RNA 1. NS4A is a cofactor for NS3 that directs the localization of NS3 and modulates its enzymatic activities 1. Glecaprevir disrupts the intracellular processes of the viral life cycle through inhibiting the NS3/4A protease activity of cleaving downstream junctions of HCV polypeptide and proteolytic processing of mature structural proteins 1.
Target Actions Organism ANS3 protease inhibitorHepatitis C Virus ANS3/4A protein inhibitorHepatitis C Virus - Absorption
In healthy subjects, the time it takes to reach the peak plasma concentration (Tmax) is approximately 5 hours. The mean peak plasma concentration (Cmax) is 597ng/mL in non-cirrhotic HCV-infected subjects. Relative to fasting conditions, the consumption of meals increases the absorption of glecaprevir by 83-163% Label.
- Volume of distribution
Not Available
- Protein binding
Pibrentasvir is 97.5% bound to human plasma proteins. The Blood-to-plasma ratio is approximately 0.57 Label.
- Metabolism
Glecaprevir undergoes limited secondary metabolism in vitro, predominantly by CYP3A Label.
- Route of elimination
The predominant route of elimination of the drug is biliary-fecal, where 92.1% of administered drug is excreted in feces and 0.7% of the drug is excreted in the urine Label.
- Half-life
The elimination half life (t1/2) is approximately 6 hours Label.
- Clearance
Not Available
- Adverse Effects
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Glecaprevir is not shown to be genotoxic according to in vitro or in vivo studies. It also shows to have no effect on mating, female or male fertility, or early embryonic development in rodent studies. Carcinogenicity studies with glecaprevir have not been conducted Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Glecaprevir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Glecaprevir. Abrocitinib The serum concentration of Glecaprevir can be increased when it is combined with Abrocitinib. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Glecaprevir. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Glecaprevir. - Food Interactions
- Avoid St. John's Wort. Co-administration may lead to decreased serum concentrations of glecaprevir.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image MAVIRET Glecaprevir (100 MG) + Pibrentasvir (40 MG) Tablet, film coated Oral Abbvie Deutschland Gmbh & Co. Kg 2017-10-05 Not applicable Italy 
Maviret Glecaprevir (100 mg) + Pibrentasvir (40 mg) Tablet Oral Abbvie 2017-09-13 Not applicable Canada 
Maviret Glecaprevir (100 mg) + Pibrentasvir (40 mg) Tablet, film coated Oral Abb Vie Deutschland Gmb H Co. Kg 2020-12-16 Not applicable EU 
Maviret Glecaprevir (50 mg / sachet) + Pibrentasvir (20 mg / sachet) Granule Oral Abbvie 2022-04-22 Not applicable Canada MAVIRET (GLECAPREVIR 100MG/ PIBRENTASVIR 40MG) FILM COATED TABLETS Glecaprevir (100 mg) + Pibrentasvir (40 mg) Tablet, film coated Oral ABBVIE SDN BHD 2020-09-08 Not applicable Malaysia 
Categories
- ATC Codes
- J05AP57 — Glecaprevir and pibrentasvir
- Drug Categories
- Acids, Acyclic
- Amides
- Amino Acids
- Amino Acids, Branched-Chain
- Amino Acids, Cyclic
- Amino Acids, Essential
- Amino Acids, Peptides, and Proteins
- Aminobutyrates
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Butyrates
- Cycloparaffins
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Direct Acting Antivirals
- HCV NS3/4A Protease Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Imino Acids
- Isobutyrates
- Lactams
- NS3/4A Protease Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 inhibitors
- OATP1B3 substrates
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- Organic Anion Transporting Polypeptide 1B3 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Sulfones
- Sulfur Compounds
- Treatments for Hepatitis C
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Cyclic peptides
- Alternative Parents
- Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Quinoxalines / Pyrrolidinecarboxamides / Alkyl aryl ethers / Pyrazines / Benzenoids / Cyclopropanecarboxylic acids and derivatives / Tertiary carboxylic acid amides show 16 more
- Substituents
- Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester show 33 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Hepatitis C Virus
Chemical Identifiers
- UNII
- K6BUU8J72P
- CAS number
- 1365970-03-1
- InChI Key
- MLSQGNCUYAMAHD-ITNVBOSISA-N
- InChI
- InChI=1S/C38H46F4N6O9S/c1-35(2,3)28-32(50)48-19-20(17-24(48)30(49)46-37(18-21(37)29(39)40)33(51)47-58(53,54)36(4)14-15-36)56-31-27(43-22-9-5-6-10-23(22)44-31)38(41,42)13-8-16-55-25-11-7-12-26(25)57-34(52)45-28/h5-6,8-10,13,20-21,24-26,28-29H,7,11-12,14-19H2,1-4H3,(H,45,52)(H,46,49)(H,47,51)/b13-8+/t20-,21+,24+,25-,26-,28-,37-/m1/s1
- IUPAC Name
- (1R,14E,18R,22R,26S,29S)-26-tert-butyl-N-[(1R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-13,13-difluoro-24,27-dioxo-2,17,23-trioxa-4,11,25,28-tetraazapentacyclo[26.2.1.0^{3,12}.0^{5,10}.0^{18,22}]hentriaconta-3,5(10),6,8,11,14-hexaene-29-carboxamide
- SMILES
- [H][C@@]12CN(C(=O)[C@@]([H])(NC(=O)O[C@]3([H])CCC[C@@]3([H])OC\C=C\C(F)(F)C3=NC4=C(C=CC=C4)N=C3O1)C(C)(C)C)[C@@]([H])(C2)C(=O)N[C@@]1(C[C@H]1C(F)F)C(=O)NS(=O)(=O)C1(C)CC1
References
- General References
- Salam KA, Akimitsu N: Hepatitis C virus NS3 inhibitors: current and future perspectives. Biomed Res Int. 2013;2013:467869. doi: 10.1155/2013/467869. Epub 2013 Oct 27. [Article]
- FDA Press Announcements: FDA approves Mavyret for Hepatitis C [Link]
- FDA Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets or pellets, for oral use [Link]
- Health Canada Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets and granules, for oral use [Link]
- External Links
- KEGG Drug
- D10814
- PubChem Compound
- 66828839
- PubChem Substance
- 347829330
- ChemSpider
- 35013015
- 1940635
- ChEMBL
- CHEMBL3545363
- ZINC
- ZINC000164528615
- PDBe Ligand
- O31
- Wikipedia
- Glecaprevir
- PDB Entries
- 6p6l / 6p6m / 6p6o / 6p6r / 6p6s / 6p6t / 6p6v / 6p6z / 6vdl / 6vdm
- FDA label
- Download (925 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Heart Transplant Infection / Hepatitis C Virus (HCV) Infection / Transplanted Kidney Complication 1 4 Completed Basic Science Cardiovascular Disease (CVD) / Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Prevention Hepatitis C Virus (HCV) Infection / Renal Failure, Chronic Renal Failure 1 4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection / Chronic Kidney Disease (CKD) 1 4 Completed Treatment Chronic Kidney Disease (CKD) / Hepatitis C Virus (HCV) Infection / Kidney Failure 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule Oral Tablet Oral Tablet, coated Oral Tablet, film coated Oral 100.0 mg Pellet Oral Tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9586978 Yes 2017-03-07 2030-12-10 US 
US8648037 Yes 2014-02-11 2032-07-19 US US9321807 Yes 2016-04-26 2035-12-05 US US8937150 Yes 2015-01-20 2032-11-18 US US10039754 Yes 2018-08-07 2030-12-10 US US10028937 Yes 2018-07-24 2030-12-10 US US10286029 Yes 2019-05-14 2034-09-14 US USRE48923 Yes 2015-11-08 2035-11-08 US US11246866 Yes 2016-12-24 2036-12-24 US US11484534 Yes 2014-09-14 2034-09-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <0.1 to 0.3 mg/mL FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0463 mg/mL ALOGPS logP 4.26 ALOGPS logP 3.95 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 3.74 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 195.22 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 194.55 m3·mol-1 Chemaxon Polarizability 78.89 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 272.7662 predictedDeepCCS 1.0 (2019) [M+H]+ 274.41943 predictedDeepCCS 1.0 (2019) [M+Na]+ 280.57626 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type peptidase activity
- Specific Function
- Not Available
- Gene Name
- Not Available
- Uniprot ID
- Q91RS4
- Uniprot Name
- NS3 protease
- Molecular Weight
- 19113.77 Da
References
- FDA Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets or pellets, for oral use [Link]
- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Heterodimer formed of a catalytic subunit (NS3) and an activating cofactor (NS4A protein)
- General Function
- Serine-type peptidase activity
- Specific Function
- Not Available
- Gene Name
- NS3/4A
- Uniprot ID
- B0B3C9
- Uniprot Name
- Genome polyprotein
- Molecular Weight
- 72789.28 Da
References
- FDA Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets or pellets, for oral use [Link]
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Glecaprevir FDA label [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
Drug created at August 31, 2017 15:33 / Updated at May 04, 2023 06:06