Dasabuvir

Identification

Summary

Dasabuviris a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.

Brand Names

Exviera, Viekira Pak

Generic Name

Dasabuvir

DrugBank Accession Number

DB09183

Background

Dasabuvir直接抗病毒药物used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients⁸．Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Dasabuvir. Dasabuvir is a non-nucleoside NS5B inhibitor which binds to the palm domain of NS5B and induces a conformational change which renders the polymerase unable to elongate viral RNA^Label．结合位点的非核苷NS5B inhibitors are poorly conserved across HCV genotypes leading to the restriction of Dasabuvir's use to genotype 1 only.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Dasabuvir as first line therapy in combination withOmbitasvir,Paritaprevir, andRitonavirfor genotype 1b and withRibavirinfor genotype 1a of Hepatitis C⁸．Dasabuvir,Ombitasvir,Paritaprevir,Ritonavir, andRibavirinare used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality⁷．

Dasabuvir is available as a fixed dose combination product withOmbitasvir,Paritaprevir, andRitonavir(tradename Viekira Pak) used for the treatment of chronic Hepatitis C. Approved in December 2014 by the FDA, Viekira Pak is indicated for the treatment of HCV genotype 1a withRibavirinor genotype 1b withoutRibavirin^Label．When combined together, DasabuvirOmbitasvir,Paritaprevir, andRitonaviras the combination product Viekira Pak have been shown to achieve a SVR of 100% for genotype 1b and 89% or 95% for genotype 1a after 12 weeks or 24 weeks of treatment includingRibavirin．

Type

Small Molecule

Groups

Approved

Structure

3D

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MOL SDF 3D-SDF PDB SMILES InChI

Similar Structures

Structure for Dasabuvir (DB09183)

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Weight

Average: 493.58
Monoisotopic: 493.167142155

Chemical Formula

C₂₆H₂₇N₃O₅S

Synonyms

• Sodium 3-(3-tert-butyl-4-methoxy-5-{6 [(methylsulfonyl)amino]naphthalene-2-yl}phenyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ide hydrate (1:1:1)
• Dasabuvir
• N-{6-[3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide

External IDs

• ABT 333
• ABT-333
• ABT333

Pharmacology

Indication

Dasabuvir, in combination withOmbitasvir,Paritaprevir, andRitonavir(as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a withRibavirinor genotype 1b withoutRibavirinincluding those with compensated cirrhosis^Label．

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Associated Conditions

• Chronic hepatitis C genotype 1a
• Chronic hepatitis C genotype 1b

Contraindications & Blackbox Warnings

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Pharmacodynamics

Dasabuvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1^Label．

Mechanism of action

Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome^Label．Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively.

By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome^6,Label．A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.

Target	Actions	Organism
ANonstructural protein 5B (NS5B)	inhibitor

Absorption

Dasabuvir reaches peak plasma concentration 4 hours after administration^Label．The absolute bioavailability of Dasabuvir is 70%.

Volume of distribution

Dasabuvir has a volume of distribution at steady state of 149 liters^Label．

Protein binding

Dasabuvir is greater than 99.5% bound to human plasma proteins^Label．

Metabolism

Dasabuvir is predominantly metabolized by CYP2C8, and to a lesser extent by CYP3A^Label．

Route of elimination

Dasabuvir is mainly excreted in the feces (94.4%) with very little excreted in the urine (2%)^Label．26.2% and 0.03% of the drug excreted in the feces and urine respectively was present as the parent compound suggesting metabolism as the major elimination pathway.

Half-life

The half-life of elimination of dasabuvir is 5.5 to 6 hours^Label．

Clearance

Clearance of Dasabuvir has not been determined.

Adverse Effects

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Toxicity

The most common adverse effects of Viekira Pak either in combination with or withoutRibavirinwere pruritus, nausea, insomnia, and asthenia^Label．

Pathways

Not Available

Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

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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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	The metabolism of Abacavir can be decreased when combined with Dasabuvir.
Abametapir	The serum concentration of Dasabuvir can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Dasabuvir can be increased when combined with Abatacept.
Abemaciclib	Dasabuvir may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abiraterone	The metabolism of Dasabuvir can be decreased when combined with Abiraterone.
Abrocitinib	The serum concentration of Dasabuvir can be increased when it is combined with Abrocitinib.
Acebutolol	The metabolism of Dasabuvir can be decreased when combined with Acebutolol.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Dasabuvir.
Adagrasib	The serum concentration of Dasabuvir can be increased when it is combined with Adagrasib.
Adalimumab	The metabolism of Dasabuvir can be increased when combined with Adalimumab.

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Food Interactions

• Avoid St. John's Wort. This herb induces the CYP3A metabolism of dasabuvir and may reduce its serum concentration. St. John's Wort is contraindicated for use with Viekira Pak.
• Take at the same time every day.
• Take with food.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Dasabuvir sodium	R2M8F5TK9T	1132940-11-4	XHGMJAKIIJSQMF-UHFFFAOYSA-M
Dasabuvir sodium monohydrate	OG6D40M62L	1456607-55-8	SJHKKWUESHNTBB-UHFFFAOYSA-M

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Exviera	Tablet, film coated	250 mg	Oral	Abbvie	2016-09-08	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Holkira Pak	Dasabuvir sodium monohydrate(250 mg)+Ombitasvir(12.5 mg)+Paritaprevir(75 mg)+Ritonavir(50 mg)	Kit; Tablet	Oral	Abbvie	2015-01-06	2018-08-15
Viekira Pak	Dasabuvir sodium monohydrate(250 mg/1)+Ombitasvir heminonahydrate(12.5 mg/1)+Paritaprevir dihydrate(75 mg/1)+Ritonavir(50 mg/1)	Kit; Tablet, film coated	Oral	AbbVie Inc.	2014-12-19	Not applicable
VIEKIRA PAK TABLET	Dasabuvir(250 mg)+Ombitasvir(12.5 mg)+Paritaprevir(75 mg)+Ritonavir(50 mg)	Tablet, film coated	Oral	ABBVIE PTE. LTD.	2015-11-02	Not applicable
Viekira XR	Dasabuvir sodium monohydrate(200 mg/1)+Ombitasvir heminonahydrate(8.33 mg/1)+Paritaprevir dihydrate(50 mg/1)+Ritonavir(33.33 mg/1)	Kit; Tablet	Oral	AbbVie Inc.	2016-07-22	2019-01-17

Categories

ATC Codes

J05AP09 — Dasabuvir

• J05AP — Antivirals for treatment of HCV infections
• J05A — DIRECT ACTING ANTIVIRALS
• J05 — ANTIVIRALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

J05AP52 — Dasabuvir, ombitasvir, paritaprevir and ritonavir

• J05AP — Antivirals for treatment of HCV infections
• J05A — DIRECT ACTING ANTIVIRALS
• J05 — ANTIVIRALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

Drug Categories

• Amides
• Amines
• Antiinfectives for Systemic Use
• Antiviral Agents
• Antivirals for Systemic Use
• Antivirals for treatment of HCV infections
• BCRP/ABCG2 Inhibitors
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 CYP2D6 Substrates
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• 细胞色素p - 450的子串ates
• Direct Acting Antivirals
• Hepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor
• Naphthalenes
• P-glycoprotein substrates
• Pyrimidines
• Pyrimidinones
• RNA Replicase Inhibitors
• Sulfones
• Sulfur Compounds
• Treatments for Hepatitis C
• UGT1A1 Inhibitors

Chemical TaxonomyProvided byClassyfire

Description

This compound belongs to the class of organic compounds known as phenylnaphthalenes. These are compounds containing a phenylnaphthalene skeleton, which consists of a naphthalene bound to a phenyl group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Naphthalenes

Sub Class

Phenylnaphthalenes

Direct Parent

Phenylnaphthalenes

Alternative Parents

Sulfanilides/Methoxyanilines/Phenylpropanes/Phenoxy compounds/Anisoles/Methoxybenzenes/Pyrimidones/Alkyl aryl ethers/Organosulfonamides/Organic sulfonamides /Hydropyrimidines/Aminosulfonyl compounds/Heteroaromatic compounds/Vinylogous amides/Lactams/Ureas/Azacyclic compounds/Hydrocarbon derivatives/Organic oxides/Organonitrogen compounds/Organopnictogen compounds

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Substituents

Alkyl aryl ether/Aminosulfonyl compound/Anisole/Aromatic heteropolycyclic compound/Azacycle/Ether/Heteroaromatic compound/Hydrocarbon derivative/Hydropyrimidine/Lactam /Methoxyaniline/Methoxybenzene/Monocyclic benzene moiety/Organic nitrogen compound/Organic oxide/有机含氧的gen compound/Organic sulfonic acid amide/Organic sulfonic acid or derivatives/Organoheterocyclic compound/Organonitrogen compound/Organooxygen compound/Organopnictogen compound/Organosulfonic acid amide/Organosulfonic acid or derivatives/Organosulfur compound/Phenol ether/Phenoxy compound/Phenylnaphthalene/Phenylpropane/Pyrimidine/Pyrimidone/Sulfanilide/Sulfonyl/Urea/Vinylogous amide

show 25 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

aromatic ether, sulfonamide, pyrimidone, ring assembly, naphthalenes (CHEBI:85182)

Affected organisms

• Hepatitis C Virus

Chemical Identifiers

UNII

DE54EQW8T1

CAS number

1132935-63-7

InChI Key

NBRBXGKOEOGLOI-UHFFFAOYSA-N

InChI

InChI=1S/C26H27N3O5S/c1-26(2,3)22-15-20(29-11-10-23(30)27-25(29)31)14-21(24(22)34-4)18-7-6-17-13-19(28-35(5,32)33)9-8-16(17)12-18/h6-15,28H,1-5H3,(H,27,30,31)

IUPAC Name

N-{6-[3-tert-butyl-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide

SMILES

COC1=C(C=C(C=C1C1=CC2=CC=C(NS(C)(=O)=O)C=C2C=C1)N1C=CC(=O)NC1=O)C(C)(C)C

References

General References

1. Gentile I, Buonomo AR, Borgia G: Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials. 2014;9(2):115-23. [Article]
2. Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [Article]
3. Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [Article]
4. McConachie SM, Wilhelm SM, Kale-Pradhan PB: New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Expert Rev Clin Pharmacol. 2016 Feb;9(2):287-302. doi: 10.1586/17512433.2016.1129272. Epub 2016 Jan 8. [Article]
5. Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [Article]
6. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [Article]
7. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
8. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]

External Links

KEGG Drug

D10582

PubChem Compound

56640146

PubChem Substance

310265091

ChemSpider

29776744

RxNav

1597381

ChEBI

85182

ChEMBL

CHEMBL3137312

ZINC

ZINC000095616937

PharmGKB

PA166163411

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Dasabuvir

FDA label

Download (540 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Hepatitis C Virus (HCV) Infection	1
4	Completed	Prevention	Hepatitis C Virus (HCV) Infection	1
4	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	3
4	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection/Chronic Kidney Disease (CKD)	1
4	Completed	Treatment	HCV Coinfection	1
4	Completed	Treatment	Hepatitis Viruses	1
4	Unknown Status	Treatment	Chronic Hepatitis C Virus (HCV) Infection	2
3	Completed	Other	Hepatitis C Virus (HCV) Infection	1
3	Completed	Treatment	Chronic Hepatitis C Genotype 1	3
3	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	10

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet, film coated	Oral	250 MG
Kit; tablet, film coated	Oral
Tablet, film coated	Oral	250 mg
Kit; tablet	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US6703403	Yes	2004-03-09	2016-12-26
US6037157	Yes	2000-03-14	2016-12-26
US7364752	Yes	2008-04-29	2021-05-10
US7148359	Yes	2006-12-12	2020-01-19
US8268349	Yes	2012-09-18	2025-02-25
US8399015	Yes	2013-03-19	2025-02-25
US9139536	No	2015-09-22	2028-11-09
US8685984	No	2014-04-01	2032-09-04
US8466159	No	2013-06-18	2032-09-04
US8642538	No	2014-02-04	2029-09-10
US8501238	No	2013-08-06	2028-09-17
US8680106	No	2014-03-25	2032-09-04
US8492386	No	2013-07-23	2032-09-04
US8188104	No	2012-05-29	2029-05-17
US9006387	No	2015-04-14	2030-06-10
US9044480	No	2015-06-02	2031-04-10
US8686026	No	2014-04-01	2031-06-09
US8420596	Yes	2013-04-16	2031-10-10
US8691938	No	2014-04-08	2032-04-13
US9629841	No	2017-04-25	2033-10-18
US9333204	No	2016-05-10	2035-01-02
US9744170	No	2017-08-29	2035-01-02
US10105365	No	2018-10-23	2035-01-02
US10201584	No	2019-02-12	2032-05-17
US10201542	No	2019-02-12	2033-10-18
US10201541	No	2019-02-12	2032-05-17

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
水溶度	0.000799 mg/mL	ALOGPS
logP	4.7	ALOGPS
logP	3.42	Chemaxon
logS	-5.8	ALOGPS
pKa (Strongest Acidic)	9.09	Chemaxon
pKa最强(基本)	-4.8	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	5	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	104.81 Å2	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	134.04 m3·mol-1	Chemaxon
Polarizability	53.19 Å3	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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insights and accelerate drug research.

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Details 1.Nonstructural protein 5B (NS5B)

Kind

Protein

Organism

Not Available

Pharmacological action

Yes

Actions

Inhibitor

General Function

Not Available

Specific Function

Rna binding

Gene Name

NS5b

Uniprot ID

P87764

Uniprot Name

Nonstructural protein 5b

分子量

Not Available

References

1. Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero JV, Poveda E, Trevino A, Barreiro P: Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013 Jun;14(9):1161-70. doi: 10.1517/14656566.2013.795543. Epub 2013 Apr 27. [Article]
2. Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [Article]
3. Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [Article]

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Drug created at October 15, 2015 18:45 / Updated at March 19, 2023 22:24