Identification

Name
Velpatasvir
Accession Number
DB11613
Type
Small Molecule
Groups
Approved
Description

Velpatasvir is a Direct-Acting Antiviral (DAA) 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]. Velpatasvir acts as a defective substrate for NS5A (Non-Structural Protein 5A), a non-enzymatic viral protein that plays a key role in Hepatitis C Virus replication, assembly, and modulation of host immune responses [3]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as velpatasvir. Notably, velpatasvir has a significantly higher barrier to resistance than the first generation NS5A inhibitors, such as Ledipasvir and Daclatasvir, making it a highly potent and reliable alternative for treatment of chronic Hepatitis C [6].

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 Velpatasvir as first line therapy in combination with sofosbuvir for all six genotypes of Hepatitis C [8]. Velpatasvir is currently only available within a fixed dose combination product as Epclusa with Sofosbuvir, another direct acting antiviral. Goals of therapy for Epclusa include the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily 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 and risk of requiring a liver transplant [5].

Since June 2016, Velpatasvir has been available as a fixed dose combination product with Sofosbuvir, as the commercially available product Epclusa. Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. It is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis and a high barrier to resistance [8]. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV [8, 5].

Structure
Thumb
Synonyms
  • methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-4-yl}-1,11-dihydro[2]benzopyrano[4',3':6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate
External IDs
GS 5816 / GS-5816 / GS5816
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EpclusaVelpatasvir (100 mg) + Sofosbuvir (400 mg)TabletOralGilead Sciences2016-08-02Not applicableCanada
EpclusaVelpatasvir (100 mg/1) + Sofosbuvir (400 mg/1)Tablet, film coatedOralGilead Sciences2016-06-28Not applicableUs
VoseviVelpatasvir (100 mg/1) + Sofosbuvir (400 mg/1) + Voxilaprevir (100 mg/1)Tablet, film coatedOralGilead Sciences2017-07-18Not applicableUs
VoseviVelpatasvir (100 mg) + Sofosbuvir (400 mg) + Voxilaprevir (100 mg)TabletOralGilead Sciences2017-09-18Not applicableCanada
Categories
UNII
KCU0C7RS7Z
CAS number
1377049-84-7
Weight
Average: 883.019
Monoisotopic: 882.406460731
Chemical Formula
C49H54N8O8
InChI Key
FHCUMDQMBHQXKK-CDIODLITSA-N
InChI
InChI=1S/C49H54N8O8/c1-26(2)41(54-48(60)63-5)47(59)57-27(3)12-17-38(57)45-51-36-16-14-30-20-35-33-15-13-31(19-32(33)25-65-40(35)21-34(30)43(36)53-45)37-22-50-44(52-37)39-18-28(24-62-4)23-56(39)46(58)42(55-49(61)64-6)29-10-8-7-9-11-29/h7-11,13-16,19-22,26-28,38-39,41-42H,12,17-18,23-25H2,1-6H3,(H,50,52)(H,51,53)(H,54,60)(H,55,61)/t27-,28-,38-,39-,41-,42+/m0/s1
IUPAC Name
(2S)-2-{[hydroxy(methoxy)methylidene]amino}-1-[(2S,5S)-2-(17-{2-[(2S,4S)-1-[(2R)-2-{[hydroxy(methoxy)methylidene]amino}-2-phenylacetyl]-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-21-oxa-5,7-diazapentacyclo[11.8.0.0^{3,11}.0^{4,8}.0^{14,19}]henicosa-1(13),2,4(8),6,9,11,14(19),15,17-nonaen-6-yl)-5-methylpyrrolidin-1-yl]-3-methylbutan-1-one
SMILES
[H][[email protected]](N=C(O)OC)(C(C)C)C(=O)N1[[email protected]@]([H])(C)CC[[email protected]@]1([H])C1=NC2=C(N1)C1=CC3=C(C=C1C=C2)C1=C(CO3)C=C(C=C1)C1=CN=C(N1)[[email protected]]1([H])C[[email protected]]([H])(COC)CN1C(=O)[[email protected]]([H])(N=C(O)OC)C1=CC=CC=C1

Pharmacology

Indication

Velpatasvir is used in combination therapy with other antiviral medications to treat chronic hepatitis C virus (HCV) infected patients with HCV genoptypes 1-6, and to treat HCV and HIV co-infected patients. Depending on the level of cirrhosis or decompensation, combination therapy can also include therapy with Ribavirin.

When used in combination with Sofosbuvir as the combination product Epclusa, Velpatasvir is 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, or in combination with Ribavirin if associated with decompensated cirrhosis [FDA Label].

Structured Indications
Pharmacodynamics

Velpatasvir is a small molecule direct-acting antiviral used in the treatment of hepatitis C in combination with sofosbuvir. Velpatasvir prevents viral replication by inhibiting non-structural protein 5A (NS5A) [4].

At a dose 5 times the recommended dose, velpatasvir does not prolong QTc interval to any clinically relevant extent [FDA Label].

Mechanism of action

Velpatasvir's mechanism of action is likely similar to other selective NS5A inhibitors which bind domain I of NS5A consisting of amino acids 33-202 [1]. NS5A inhibitors compete with RNA for binding at this site. It is also thought that NS5A inhibitors bind the target during its action in replication when the binding site is exposed [2]. Inhibition of NS5A is also known to produce redistribution of the protein to lipid droplets. The exact role of NS5A in RNA replication is not yet understood although it is known to be an important component.

TargetActionsOrganism
ANonstructural Protein 5A (NS5A)
inhibitor
Hepatitis C Virus (HCV)
Absorption

Oral bioavailability of 25-30% [3].

Volume of distribution

1.4-1.6 L/kg [3].

Protein binding

>99.5% bound to plasma proteins [FDA Label].

Metabolism

Some metabolism by CYP2B6, CYP2C8, and CYP3A4 [3].

Route of elimination

94% excreted in feces with 77% as parent compound. 0.4% excreted in urine [FDA Label].

Half life

15h [FDA Label].

Clearance

Estimated 0.12 L/h/kg [A19175.

Toxicity

No indication of carcinogenicity or impairment of fertility/fetal viability [FDA Label].

Affected organisms
  • Hepatitis C Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Velpatasvir can be increased when it is combined with Abiraterone.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Velpatasvir.Approved
AmiodaroneThe metabolism of Velpatasvir can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Velpatasvir can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Velpatasvir can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Velpatasvir can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of Velpatasvir can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Velpatasvir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Velpatasvir can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Velpatasvir.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Velpatasvir.Approved
CarbamazepineThe metabolism of Velpatasvir can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Velpatasvir can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Velpatasvir can be increased when it is combined with Ceritinib.Approved
CitalopramThe metabolism of Velpatasvir can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Velpatasvir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Velpatasvir can be decreased when combined with Clemastine.Approved
ClopidogrelThe metabolism of Velpatasvir can be decreased when combined with Clopidogrel.Approved, Nutraceutical
ClotrimazoleThe metabolism of Velpatasvir can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Velpatasvir can be decreased when combined with Cobicistat.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Velpatasvir.Approved
ConivaptanThe serum concentration of Velpatasvir can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Velpatasvir can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Velpatasvir can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Velpatasvir can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Velpatasvir.Approved
DabrafenibThe serum concentration of Velpatasvir can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Velpatasvir can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Velpatasvir can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Velpatasvir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Velpatasvir can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Velpatasvir can be decreased when combined with Desipramine.Approved
DihydroergotamineThe metabolism of Velpatasvir can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Velpatasvir can be decreased when combined with Diltiazem.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Velpatasvir.Approved, Investigational
DoxorubicinThe metabolism of Velpatasvir can be decreased when combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Velpatasvir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Velpatasvir can be decreased when combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Velpatasvir.Approved
EfavirenzThe metabolism of Velpatasvir can be decreased when combined with Efavirenz.Approved, Investigational
EltrombopagThe serum concentration of Velpatasvir can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Velpatasvir can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Velpatasvir can be decreased when combined with Erythromycin.Approved, Vet Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Velpatasvir.Approved
FelodipineThe metabolism of Velpatasvir can be decreased when combined with Felodipine.Approved, Investigational
FluconazoleThe metabolism of Velpatasvir can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Velpatasvir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Velpatasvir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Velpatasvir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Velpatasvir can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Velpatasvir can be increased when it is combined with Fusidic Acid.Approved
ImatinibThe metabolism of Velpatasvir can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Velpatasvir can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Velpatasvir can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Velpatasvir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Velpatasvir can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Velpatasvir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Velpatasvir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Velpatasvir can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibThe metabolism of Velpatasvir can be decreased when combined with Lapatinib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Velpatasvir.Approved
LopinavirThe metabolism of Velpatasvir can be decreased when combined with Lopinavir.Approved
LosartanThe metabolism of Velpatasvir can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Velpatasvir can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Velpatasvir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Velpatasvir can be increased when it is combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Velpatasvir can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Velpatasvir can be decreased when it is combined with Mitotane.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Velpatasvir.Approved
NefazodoneThe metabolism of Velpatasvir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Velpatasvir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Velpatasvir can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Velpatasvir can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Velpatasvir can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Velpatasvir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Velpatasvir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Velpatasvir can be increased when it is combined with Palbociclib.Approved
ParoxetineThe metabolism of Velpatasvir can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Velpatasvir.Approved
PentobarbitalThe metabolism of Velpatasvir can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Velpatasvir can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Velpatasvir can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Velpatasvir can be decreased when combined with Pioglitazone.Approved, Investigational
PosaconazoleThe metabolism of Velpatasvir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Velpatasvir can be increased when combined with Primidone.Approved, Vet Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Velpatasvir.Approved
QuazepamThe serum concentration of Velpatasvir can be increased when it is combined with Quazepam.Approved, Illicit
QuinineThe metabolism of Velpatasvir can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Velpatasvir can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Velpatasvir.Approved, Investigational
RifabutinThe metabolism of Velpatasvir can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Velpatasvir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Velpatasvir can be increased when combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Velpatasvir.Approved, Investigational
RolapitantThe serum concentration of Velpatasvir can be increased when it is combined with Rolapitant.Approved
RosiglitazoneThe metabolism of Velpatasvir can be decreased when combined with Rosiglitazone.Approved, Investigational
SaquinavirThe metabolism of Velpatasvir can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Velpatasvir can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Velpatasvir can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Velpatasvir can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Velpatasvir.Approved
SiltuximabThe serum concentration of Velpatasvir can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Velpatasvir can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Velpatasvir can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Velpatasvir can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Velpatasvir can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleThe metabolism of Velpatasvir can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Velpatasvir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamoxifenThe metabolism of Velpatasvir can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Velpatasvir can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Velpatasvir can be decreased when combined with Telithromycin.Approved
TeriflunomideThe serum concentration of Velpatasvir can be increased when it is combined with Teriflunomide.Approved
ThiotepaThe metabolism of Velpatasvir can be decreased when combined with Thiotepa.Approved
TiclopidineThe metabolism of Velpatasvir can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Velpatasvir can be decreased when it is combined with Tocilizumab.Approved
TopiroxostatThe metabolism of Velpatasvir can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Velpatasvir.Approved, Investigational
TrimethoprimThe metabolism of Velpatasvir can be decreased when combined with Trimethoprim.Approved, Vet Approved
VenlafaxineThe metabolism of Velpatasvir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Velpatasvir can be decreased when combined with Verapamil.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Velpatasvir.Approved, Investigational
VoriconazoleThe metabolism of Velpatasvir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Velpatasvir can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Ascher DB, Wielens J, Nero TL, Doughty L, Morton CJ, Parker MW: Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA. Sci Rep. 2014 Apr 23;4:4765. doi: 10.1038/srep04765. [PubMed:24755925]
  2. Targett-Adams P, Graham EJ, Middleton J, Palmer A, Shaw SM, Lavender H, Brain P, Tran TD, Jones LH, Wakenhut F, Stammen B, Pryde D, Pickford C, Westby M: Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action. J Virol. 2011 Jul;85(13):6353-68. doi: 10.1128/JVI.00215-11. Epub 2011 Apr 20. [PubMed:21507963]
  3. Mogalian E, German P, Kearney BP, Yang CY, Brainard D, Link J, McNally J, Han L, Ling J, Mathias A: Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02084-16. doi: 10.1128/AAC.02084-16. Print 2017 May. [PubMed:28193657]
  4. Lawitz E, Freilich B, Link J, German P, Mo H, Han L, Brainard DM, McNally J, Marbury T, Rodriguez-Torres M: A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus. J Viral Hepat. 2015 Dec;22(12):1011-9. doi: 10.1111/jvh.12435. Epub 2015 Jul 16. [PubMed:26183611]
  5. 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]
  6. Lawitz EJ, Dvory-Sobol H, Doehle BP, Worth AS, McNally J, Brainard DM, Link JO, Miller MD, Mo H: Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5368-78. doi: 10.1128/AAC.00763-16. Print 2016 Sep. [PubMed:27353271]
  7. Epclusa FDA Approval Announcement [Link]
  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
D10806
PubChem Compound
67683363
PubChem Substance
347828007
ChemSpider
34501056
ChEBI
133009
ChEMBL
CHEMBL3545062
PharmGKB
PA166163415
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Velpatasvir
FDA label
Download (338 KB)
MSDS
Download (243 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentChronic Hepatitis C Infection / Lung Transplant Infection1
0RecruitingTreatmentChronic Hepatitis C Infection / Transplant, Kidney1
1CompletedTreatmentChronic Hepatitis C Virus1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentHepatitis C Virus (HCV)1
1CompletedTreatmentHepatitis C Virus Infection1
2CompletedTreatmentChronic Hepatitis C Infection2
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection2
2CompletedTreatmentHepatitis C Virus Infection6
2RecruitingTreatmentChronic Hepatitis C Infection1
2RecruitingTreatmentChronic Hepatitis C Infection / Indolent B-cell Lymphoma1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection3
2RecruitingTreatmentHepatitis C Virus Infection3
3Active Not RecruitingTreatmentHepatitis C Virus Infection4
3CompletedTreatmentChronic Hepatitis C Infection2
3CompletedTreatmentHepatitis C Virus Infection10
4CompletedTreatmentHepatitis C Virus Infection, Response to Therapy of / Human Immunodeficiency Virus (HIV)1
4Enrolling by InvitationTreatmentHepatitis C, Chronic1
4Not Yet RecruitingHealth Services ResearchHepatitis C, Chronic / Opioid-use Disorder1
4Not Yet RecruitingPreventionChronic Hepatitis C Infection1
4Not Yet RecruitingPreventionChronic Hepatitis C Infection / End Stage Liver Diseases1
4Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Hepatitis C, Chronic / Opiate Dependence1
4RecruitingTreatmentAwaiting Organ Transplant / Chronic Hepatitis C Infection1
4RecruitingTreatmentChronic Hepatitis C Infection1
4RecruitingTreatmentChronic Hepatitis C Infection / Thalassaemic disorders1
4RecruitingTreatmentHCV Coinfection / Human Immunodeficiency Virus (HIV) / Liver Diseases1
4RecruitingTreatmentHepatitis C, Chronic / Lung Transplant1
Not AvailableEnrolling by InvitationNot AvailableChronic Hepatitis C Infection1
Not AvailableNot Yet RecruitingTreatmentCardiac Transplant / Chronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7964580No2009-03-262029-03-26Us
US8334270No2008-03-212028-03-21Us
US8633309No2009-03-262029-03-26Us
US8618076No2010-12-112030-12-11Us
US8735372No2008-03-212028-03-21Us
US8580765No2008-03-212028-03-21Us
US8889159No2009-03-262029-03-26Us
US9085573No2008-03-212028-03-21Us
US9284342No2010-09-132030-09-13Us
US8940718No2012-11-162032-11-16Us
US8575135No2012-11-162032-11-16Us
US8921341No2012-11-162032-11-16Us
US9585906No2008-03-212028-03-21Us
US9296782No2014-07-172034-07-17Us
US9757406No2014-01-302034-01-30Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00153 mg/mLALOGPS
logP5.65ALOGPS
logP4.26ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)3.74ChemAxon
pKa (Strongest Basic)5.98ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area200.08 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity242.15 m3·mol-1ChemAxon
Polarizability97.91 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthopyrans. These are compounds containing a pyran ring fused to a naphthalene moiety. Furan is a 6 membered-ring non-aromatic ring with five carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Naphthopyrans
Sub Class
Not Available
Direct Parent
Naphthopyrans
Alternative Parents
Dibenzopyrans / Valine and derivatives / Alpha amino acid amides / Phenylacetamides / 2-benzopyrans / Naphthalenes / Benzimidazoles / N-acylpyrrolidines / Alkyl aryl ethers / Pyrans
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Substituents
Naphthopyran / Dibenzopyran / Valine or derivatives / Alpha-amino acid amide / Naphthalene / Phenylacetamide / 1-benzopyran / 2-benzopyran / Benzopyran / Alpha-amino acid or derivatives
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

1. Nonstructural Protein 5A (NS5A)
Kind
Protein
Organism
Hepatitis C Virus (HCV)
Pharmacological action
Yes
Actions
Inhibitor

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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
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
Human
Pharmacological action
No
Actions
Substrate
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 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
Human
Pharmacological action
No
Actions
Inhibitor
Transporter
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
Human
Pharmacological action
No
Actions
Inhibitor
Transporter
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
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
Transporter
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da

Drug created on August 05, 2016 17:48 / Updated on December 01, 2017 16:22