Identification
NameDasabuvir
Accession NumberDB09183
TypeSmall Molecule
GroupsApproved
Description

Dasabuvir is a direct acting antiviral medication 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 patients [8]. 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 [FDA Label]. The binding sites for non-nucleoside 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 with Ombitasvir, Paritaprevir, and Ritonavir for genotype 1b and with Ribavirin for genotype 1a of Hepatitis C [8]. Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir, and Ribavirin are 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 mortality [7].

Dasabuvir is available as a fixed dose combination product with Ombitasvir, Paritaprevir, and Ritonavir (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 with Ribavirin or genotype 1b without Ribavirin [FDA Label]. When combined together, Dasabuvir Ombitasvir, Paritaprevir, and Ritonavir as 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 including Ribavirin.

Structure
Thumb
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)
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
Product Ingredients
IngredientUNIICASInChI KeyDetails
Dasabuvir sodiumR2M8F5TK9T 1132940-11-4XHGMJAKIIJSQMF-UHFFFAOYSA-MDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ExvieraTablet, film coated250 mgOralAbbvie2015-01-15Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Holkira PakKit; TabletOralAbbvie2015-01-06Not applicableCanada
Viekira PakKitAbbvie2014-12-19Not applicableUs
Viekira XRKitAbbvie2016-07-22Not applicableUs
Categories
UNIIDE54EQW8T1
CAS number1132935-63-7
WeightAverage: 493.58
Monoisotopic: 493.167142155
Chemical FormulaC26H27N3O5S
InChI KeyNBRBXGKOEOGLOI-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
Pharmacology
Indication

Dasabuvir, in combination with Ombitasvir, Paritaprevir, and Ritonavir (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin including those with compensated cirrhosis [FDA Label].

Structured Indications
Pharmacodynamics

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

TargetKindPharmacological actionActionsOrganismUniProt ID
Nonstructural protein 5B (NS5B)Proteinyes
inhibitor
P87764 details
Related Articles
Absorption

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

Volume of distribution

Dasabuvir has a volume of distribution at steady state of 149 liters [FDA Label].

Protein binding

Dasabuvir is greater than 99.5% bound to human plasma proteins [FDA Label].

Metabolism

Dasabuvir is predominantly metabolized by CYP2C8, and to a lesser extent by CYP3A [FDA Label].

Route of elimination

Dasabuvir is mainly excreted in the feces (94.4%) with very little excreted in the urine (2%) [FDA 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 [FDA Label].

Clearance

Clearance of Dasabuvir has not been determined.

Toxicity

The most common adverse effects of Viekira Pak either in combination with or without Ribavirin were pruritus, nausea, insomnia, and asthenia [FDA Label].

Affected organisms
  • Hepatitis C Virus
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Dasabuvir can be increased when it is combined with Abiraterone.Approved
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Dasabuvir.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational
AmiodaroneThe serum concentration of Amiodarone can be increased when it is combined with Dasabuvir.Approved, Investigational
AprepitantThe serum concentration of Dasabuvir can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Dasabuvir can be decreased when combined with Artemether.Approved
AtazanavirThe serum concentration of Dasabuvir can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Dasabuvir can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Dasabuvir.Approved
BetaxololThe metabolism of Dasabuvir can be decreased when combined with Betaxolol.Approved
BexaroteneThe serum concentration of Dasabuvir can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Dasabuvir can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Dasabuvir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Dasabuvir can be decreased when it is combined with Bosentan.Approved, Investigational
BuprenorphineThe serum concentration of Buprenorphine can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Dasabuvir can be decreased when combined with Bupropion.Approved
CarbamazepineThe serum concentration of Dasabuvir can be decreased when it is combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Dasabuvir can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Dasabuvir can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Dasabuvir can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Dasabuvir can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Dasabuvir can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Dasabuvir can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Dasabuvir can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Dasabuvir can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Dasabuvir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Dasabuvir can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Dasabuvir can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Dasabuvir can be decreased when combined with Clomipramine.Approved, Vet Approved
ClopidogrelThe serum concentration of Dasabuvir can be increased when it is combined with Clopidogrel.Approved, Nutraceutical
ClotrimazoleThe metabolism of Dasabuvir can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Dasabuvir can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Dasabuvir can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Dasabuvir can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Dasabuvir can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Dasabuvir can be decreased when combined with Crizotinib.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Dasabuvir.Approved, Investigational, Vet Approved
CyclosporineThe metabolism of Dasabuvir can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Dasabuvir can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Dasabuvir can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Darunavir can be decreased when it is combined with Dasabuvir.Approved
DasatinibThe serum concentration of Dasabuvir can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Dasabuvir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Dasabuvir can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Dasabuvir can be decreased when combined with Desipramine.Approved
DexamethasoneThe serum concentration of Dasabuvir can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Dasabuvir can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Dasabuvir can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Dasabuvir can be decreased when combined with Diphenhydramine.Approved
DoxycyclineThe metabolism of Dasabuvir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Dasabuvir can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Dasabuvir can be decreased when combined with Duloxetine.Approved
EfavirenzThe serum concentration of Dasabuvir can be decreased when it is combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Dasabuvir can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Dasabuvir can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Dasabuvir can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Dasabuvir can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Dasabuvir can be decreased when it is combined with Etravirine.Approved
FelodipineThe metabolism of Dasabuvir can be decreased when combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational, Vet Approved
FluconazoleThe metabolism of Dasabuvir can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Dasabuvir can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Dasabuvir.Approved
FluvoxamineThe metabolism of Dasabuvir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Dasabuvir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Dasabuvir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Dasabuvir can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Dasabuvir can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe serum concentration of Dasabuvir can be increased when it is combined with Gemfibrozil.Approved
HaloperidolThe metabolism of Dasabuvir can be decreased when combined with Haloperidol.Approved
IdelalisibThe serum concentration of Dasabuvir can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Dasabuvir can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Dasabuvir can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Dasabuvir can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Dasabuvir can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Dasabuvir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Dasabuvir can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Dasabuvir can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Dasabuvir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Dasabuvir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Dasabuvir can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibThe metabolism of Dasabuvir can be decreased when combined with Lapatinib.Approved, Investigational
LopinavirThe serum concentration of Dasabuvir can be increased when it is combined with Lopinavir.Approved
LorcaserinThe metabolism of Dasabuvir can be decreased when combined with Lorcaserin.Approved
LosartanThe metabolism of Dasabuvir can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Dasabuvir can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Dasabuvir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Dasabuvir can be increased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Dasabuvir can be decreased when combined with Lumefantrine.Approved
MethadoneThe metabolism of Dasabuvir can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Dasabuvir can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Dasabuvir can be decreased when combined with Metoprolol.Approved, Investigational
MifepristoneThe serum concentration of Dasabuvir can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Dasabuvir can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Dasabuvir can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Dasabuvir can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Dasabuvir can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe metabolism of Dasabuvir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Dasabuvir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Dasabuvir can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Dasabuvir can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Dasabuvir can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Dasabuvir can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Dasabuvir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Dasabuvir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Dasabuvir can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Dasabuvir can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Dasabuvir can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Dasabuvir.Approved
Peginterferon alfa-2bThe serum concentration of Dasabuvir can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Dasabuvir can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe serum concentration of Dasabuvir can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Dasabuvir can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Dasabuvir can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Dasabuvir.Approved
PosaconazoleThe metabolism of Dasabuvir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Dasabuvir can be decreased when it is combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Dasabuvir can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Dasabuvir.Approved
QuinineThe metabolism of Dasabuvir can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Dasabuvir can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe metabolism of Dasabuvir can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Dasabuvir can be increased when combined with Rifabutin.Approved
RifampicinThe serum concentration of Dasabuvir can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Dasabuvir can be decreased when it is combined with Rifapentine.Approved
RitonavirThe serum concentration of Dasabuvir can be increased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Dasabuvir can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Dasabuvir can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Dasabuvir can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Dasabuvir.Approved
SaquinavirThe metabolism of Dasabuvir can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe serum concentration of Dasabuvir can be decreased when it is combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Dasabuvir can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Dasabuvir can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Dasabuvir can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Dasabuvir can be increased when it is combined with Simeprevir.Approved
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Dasabuvir.Approved, Investigational
St. John's WortThe serum concentration of Dasabuvir can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Dasabuvir can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleThe metabolism of Dasabuvir can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Dasabuvir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Dasabuvir.Approved, Investigational
TamoxifenThe metabolism of Dasabuvir can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Dasabuvir can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Dasabuvir can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Dasabuvir can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe metabolism of Dasabuvir can be decreased when combined with Teriflunomide.Approved
ThioridazineThe metabolism of Dasabuvir can be decreased when combined with Thioridazine.Withdrawn
TiclopidineThe metabolism of Dasabuvir can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Dasabuvir can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Dasabuvir can be decreased when it is combined with Tocilizumab.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Dasabuvir.Approved, Investigational
TranylcypromineThe metabolism of Dasabuvir can be decreased when combined with Tranylcypromine.Approved
TrimethoprimThe metabolism of Dasabuvir can be decreased when combined with Trimethoprim.Approved, Vet Approved
VenlafaxineThe metabolism of Dasabuvir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Dasabuvir can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Dasabuvir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Dasabuvir can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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. [PubMed:24882169 ]
  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. [PubMed:25665437 ]
  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. [PubMed:26567871 ]
  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. [PubMed:26651915 ]
  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. [PubMed:27179126 ]
  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. [PubMed:28497432 ]
  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. [PubMed:25585348 ]
  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
ATC CodesJ05AX16 — DasabuvirJ05AX66 — Dasabuvir, ombitasvir, paritaprevir and ritonavir
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (540 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHCV Infections3
1CompletedNot AvailableRelative Bioavailability1
1CompletedTreatmentHCV Infections2
1CompletedTreatmentHealthy Volunteers1
2CompletedNot AvailableHCV Infections1
2CompletedTreatmentChronic Hepatitis C Infection3
2CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Infection / HCV / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus Infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection Genotype 12
3Active Not RecruitingTreatmentHepatitis C, Acute1
3CompletedNot AvailableChronic Hepatitis C Infection1
3CompletedTreatmentChronic Hepatitis C Infection10
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Kidney Disease (CKD) / Genotype 1a / Genotype 4 / HCV / IFN / PegIFN1
3CompletedTreatmentChronic Hepatitis C Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus2
3CompletedTreatmentChronic Hepatitis C Virus (HCV Infection Genotype 1)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Cirrhosis, Decompensated / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated Cirrhosis and Non-cirrhotics / Hepatitis C Virus Infection / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / End-Stage Renal Disease (ESRD) / Hepatitis C Virus (HCV) / Severe Renal Impairment1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C Virus (HCV) / Liver Cirrhosis1
3CompletedTreatmentHepatitis C Infection / Hepatitis C Virus (HCV)1
3RecruitingTreatmentChronic Hepatitis C Infection1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV)1
4Active Not RecruitingTreatmentHepatitis C, Chronic1
4Not Yet RecruitingTreatmentChronic Hepatitis, C Virus1
4Not Yet RecruitingTreatmentHCV Coinfection1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4RecruitingTreatmentHepatitis C, Chronic1
4RecruitingTreatmentHepatitis Viruses1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral250 mg
Kit; tabletOral
Kit
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6703403 Yes1996-12-262016-12-26Us
US6037157 Yes1996-12-262016-12-26Us
US7364752 Yes2001-05-102021-05-10Us
US7148359 Yes2000-01-192020-01-19Us
US8268349 Yes2005-02-252025-02-25Us
US8399015 Yes2005-02-252025-02-25Us
US9139536 No2008-11-092028-11-09Us
US8685984 No2012-09-042032-09-04Us
US8466159 No2012-09-042032-09-04Us
US8642538 No2009-09-102029-09-10Us
US8501238 No2008-09-172028-09-17Us
US8680106 No2012-09-042032-09-04Us
US8492386 No2012-09-042032-09-04Us
US8188104 No2009-05-172029-05-17Us
US9006387 No2010-06-102030-06-10Us
US9044480 No2011-04-102031-04-10Us
US8686026 No2011-06-092031-06-09Us
US8420596 Yes2011-10-102031-10-10Us
US8691938 No2012-04-132032-04-13Us
US9629841 No2013-10-182033-10-18Us
US9333204 No2015-01-022035-01-02Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000799 mg/mLALOGPS
logP4.7ALOGPS
logP3.42ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area104.81 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity134.04 m3·mol-1ChemAxon
Polarizability53.19 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassPhenylnaphthalenes
Direct ParentPhenylnaphthalenes
Alternative ParentsSulfanilides / Methoxyanilines / Phenylpropanes / Phenoxy compounds / Anisoles / Methoxybenzenes / Pyrimidones / Alkyl aryl ethers / Organosulfonamides / Organic sulfonamides
SubstituentsPhenylnaphthalene / Sulfanilide / Phenylpropane / Methoxyaniline / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Pyrimidone
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsaromatic ether, sulfonamide, pyrimidone, ring assembly, naphthalenes (CHEBI:85182 )

Targets

Kind
Protein
Organism
Pharmacological action
yes
Actions
inhibitor
General Function:
Not Available
Specific Function:
Rna binding
Gene Name:
NS5b
Uniprot ID:
P87764
Uniprot Name:
Nonstructural protein 5b
Molecular Weight:
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. [PubMed:23621117 ]
  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. [PubMed:26567871 ]
  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. [PubMed:25665437 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Uniprot Name:
Cytochrome P450 2C8
Molecular Weight:
55824.275 Da
References
  1. 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. [PubMed:27179126 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. 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. [PubMed:27179126 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Uniprot Name:
Cytochrome P450 2D6
Molecular Weight:
55768.94 Da
References
  1. 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. [PubMed:27179126 ]
4. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Uniprot Name:
ATP-binding cassette sub-family G member 2
Molecular Weight:
72313.47 Da
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Efflux transmembrane transporter activity
Specific Function:
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug doxorubicin. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair.
Gene Name:
ABCB5
Uniprot ID:
Q2M3G0
Uniprot Name:
ATP-binding cassette sub-family B member 5
Molecular Weight:
138639.48 Da
Drug created on October 15, 2015 12:45 / Updated on August 08, 2017 11:11