U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H52F4N6O9S
Molecular Weight 868.9369
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VOXILAPREVIR

SMILES

CC[C@]1([H])[C@]2([H])CN([C@]1([H])C(=N[C@@]3(C[C@@]3([H])C(F)F)C(=NS(=O)(=O)C4(C)CC4)O)O)C(=O)[C@]([H])(C(C)(C)C)N=C(O)O[C@]5([H])C[C@@]5([H])CCCCC(c6c(nc7cc(ccc7n6)OC)O2)(F)F

InChI

InChIKey=MZBLZLWXUBZHSL-FZNJKFJKSA-N
InChI=1S/C40H52F4N6O9S/c1-7-22-27-19-50(28(22)32(51)48-39(18-23(39)31(41)42)35(53)49-60(55,56)38(5)14-15-38)34(52)30(37(2,3)4)47-36(54)59-26-16-20(26)10-8-9-13-40(43,44)29-33(58-27)46-25-17-21(57-6)11-12-24(25)45-29/h11-12,17,20,22-23,26-28,30-31H,7-10,13-16,18-19H2,1-6H3,(H,47,54)(H,48,51)(H,49,53)/t20-,22-,23+,26-,27+,28+,30-,39-/m1/s1

HIDE SMILES / InChI

Molecular Formula C40H52F4N6O9S
Molecular Weight 868.9369
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Voxilaprevir 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). Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) is indicated for adult patients with chronic HCV without cirrhosis or with compensated cirrhosis who have (1) genotype 1 through 6 and have previously been treated with an NS5A inhibitor or (2) genotype 1a or 3 and have previously been treated with sofosbuvir without an NS5A inhibitor. Voxilaprevir exerts its antiviral action by reversibley binding and inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV). Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B. By inhibiting viral protease NS3/4A, voxilaprevir therefore prevents viral replication and function.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VOSEVI

Approved Use

VOSEVI is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, velpatasvir, an HCV NS5A inhibitor, and voxilaprevir, an HCV NS3/4A protease inhibitor, and is indicated for the treatment of adult patients with chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have (1, 2.2, 14):  genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor.  genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. o Additional benefit of VOSEVI over sofosbuvir/velpatasvir was not shown in adults with genotype 1b, 2, 4, 5, or 6 infection previously treated with sofosbuvir without an NS5A inhibitor.

Launch Date

1500249600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
156.7 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
155.1 ng/mL
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
28.6 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
39.8 ng/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
413.8 ng/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
70.4 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1227 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1357.6 ng × h/mL
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
183.3 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
372.3 ng × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3926.9 ng × h/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
479.2 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.8 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
37.28 h
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
11.87 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
39.71 h
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
30.33 h
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
11.18 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VOXILAPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
unknown, unknown
VOXILAPREVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, 43 years (range: 30–56 years)
Health Status: unhealthy
Age Group: 43 years (range: 30–56 years)
Sex: M+F
Sources:
Other AEs: Diarrhoea...
Other AEs:
Diarrhoea (6.7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Diarrhoea 6.7%
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, 43 years (range: 30–56 years)
Health Status: unhealthy
Age Group: 43 years (range: 30–56 years)
Sex: M+F
Sources:
PubMed

PubMed

TitleDatePubMed
IFNL4 Genotype Is Associated With Virologic Relapse After 8-Week Treatment With Sofosbuvir, Velpatasvir, and Voxilaprevir.
2017 Dec
Betrixaban, sofosbuvir/velpatasvir/voxilaprevir, and glecaprevir/pibrentasvir.
2017 Nov - Dec
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: Recommended dosage: One tablet (400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir) taken orally once daily with food. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209195Orig1s000lbl.pdf
The safety, tolerability, antiviral activity and pharmacokinetics (PK) of Voxilaprevir (GS-9857) were evaluated in patients with chronic HCV genotype 1-4 infection. Patients with genotype 1-4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions.
Route of Administration: Oral
Voxilaprevir (VOX) had EC50s against HCV replicons 1b, 2a, 4a, 4d, 5a, and 6a of between 1.21 and 3.25 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:42:09 UTC 2021
Edited
by admin
on Sat Jun 26 07:42:09 UTC 2021
Record UNII
0570F37359
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VOXILAPREVIR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
8H-7,10-METHANOCYCLOPROPA(18,19)(1,10,3,6)DIOXADIAZACYCLONONADECINO(11,12-B)QUINOXALINE-8-CARBOXAMIDE, N-((1R,2R)-2-(DIFLUOROMETHYL)-1-((((1-METHYLCYCLOPROPYL)SULFONYL)AMINO)CARBONYL)CYCLOPROPYL)-5-(1,1-DIMETHYLETHYL)-9-ETHYL-18,18-DIFLUORO-1,1A,3,4,5,6,
Systematic Name English
VOXILAPREVIR [ORANGE BOOK]
Common Name English
VOXILAPREVIR COMPONENT OF VOSEVI
Common Name English
VOXILAPREVIR [MI]
Common Name English
VOXILAPREVIR [INN]
Common Name English
VOSEVI COMPONENT VOXILAPREVIR
Common Name English
VOXILAPREVIR [USAN]
Common Name English
VOXILAPREVIR [WHO-DD]
Common Name English
GS-9857
Code English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
NDF-RT N0000182639
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
NCI_THESAURUS C281
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
WHO-ATC J05AP56
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C152922
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
RXCUI
1939323
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
CAS
1535212-07-7
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
FDA UNII
0570F37359
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
INN
10143
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
MERCK INDEX
M12017
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
DRUG CENTRAL
5242
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
ChEMBL
CHEMBL3707372
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
EVMPD
SUB185303
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
PUBCHEM
89921642
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
LACTMED
Voxilaprevir
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
DRUG BANK
DB12026
Created by admin on Sat Jun 26 07:42:09 UTC 2021 , Edited by admin on Sat Jun 26 07:42:09 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
IC50
TRANSPORTER -> SUBSTRATE
IC50
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
inhibit 6.7% at 10 ?M
IC50
Related Record Type Details
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
FECAL
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC