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
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

1.50024959E12
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)
n = 15
Health Status: unhealthy
Condition: C virus genotype 1–4 infection
Age Group: 43 years (range: 30–56 years)
Sex: M+F
Population Size: 15
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)
n = 15
Health Status: unhealthy
Condition: C virus genotype 1–4 infection
Age Group: 43 years (range: 30–56 years)
Sex: M+F
Population Size: 15
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
Characterization of HCV resistance from a 3-day monotherapy study of voxilaprevir, a novel pangenotypic NS3/4A protease inhibitor.
2018
Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C.
2018 Apr
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.
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