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

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H52F4N6O9S
Molecular Weight 868.934
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VOXILAPREVIR

SMILES

[H][C@]12CN([C@@H]([C@@H]1CC)C(=O)N[C@@]3(C[C@H]3C(F)F)C(=O)NS(=O)(=O)C4(C)CC4)C(=O)[C@@H](NC(=O)O[C@@H]5C[C@H]5CCCCC(F)(F)C6=NC7=CC=C(OC)C=C7N=C6O2)C(C)(C)C

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 868.934
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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.

Originator

Approval Year

2017
422
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 38.0 pM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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

2017
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
156.7 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26957110
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%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209195s003lbl.pdf
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:
https://pubmed.ncbi.nlm.nih.gov/26957110
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:
https://pubmed.ncbi.nlm.nih.gov/26957110
Other AEs: Diarrhoea...
Other AEs:
Diarrhoea (6.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26957110
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:
https://pubmed.ncbi.nlm.nih.gov/26957110
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:
https://pubmed.ncbi.nlm.nih.gov/26957110
Sourcing

Sourcing

Vendor/AggregatorIDURL
Chem Scene
CS-0017027
http://www.chemscene.com/1535212-07-7.html
Compound Cloud
89921642
DC Chemicals
DC21072
http://www.dcchemicals.com//product_show-DC21072.html
DC Chemicals
Voxilaprevir
http://www.dcchemicals.com/product_show-DC21072.html
Lan Pharmatech
LAN-B79277
MedChem Express
HY-19840
https://www.medchemexpress.com/voxilaprevir.html
Molnova
M12165
MuseChem
I010171
https://www.musechem.com/product/I010171.html
PI Chemicals
PI-42354
Smolecule
S546873
http://www.smolecule.com/products/s546873
THE BioTek
bt-286497
https://www.thebiotek.com/product/inhibitors/bt-286497
ZINC
ZINC000218037687
http://zinc15.docking.org/substances/ZINC000218037687
eNovation Chemicals
D671519
https://www.enovationchem.com/ProductDetails.asp?ProductID=D671519
mcule
MCULE-6858232909
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
Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C.
2018 Apr
Patents

Patents

US20130157973
1
WO2014008285
1

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
In Vitro Use Guide
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 Dec 16 09:39:01 GMT 2023
Edited
by admin
on Sat Dec 16 09:39:01 GMT 2023
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 [WHO-DD]
Common Name English
voxilaprevir [INN]
Common Name English
VOSEVI COMPONENT VOXILAPREVIR
Common Name English
VOXILAPREVIR [USAN]
Common Name English
GS-9857
Code English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
NDF-RT N0000182639
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
NCI_THESAURUS C281
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
WHO-ATC J05AP56
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C152922
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
RXCUI
1939323
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
WIKIPEDIA
Voxilaprevir
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
CAS
1535212-07-7
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
USAN
DE-46
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
FDA UNII
0570F37359
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
INN
10143
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
MERCK INDEX
m12017
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
EPA CompTox
DTXSID301027947
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
DRUG CENTRAL
5242
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
ChEMBL
CHEMBL3707372
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
SMS_ID
100000171342
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
EVMPD
SUB185303
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
PUBCHEM
89921642
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
LACTMED
Voxilaprevir
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
DAILYMED
0570F37359
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
DRUG BANK
DB12026
Created by admin on Sat Dec 16 09:39:01 GMT 2023 , Edited by admin on Sat Dec 16 09:39:01 GMT 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
Structure of VOXILAPREVIR
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
HCV NS3-4A SERINE PROTEASE
TARGET -> INHIBITOR
OATP-8
TRANSPORTER -> SUBSTRATE
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
OATP1B1
TRANSPORTER -> SUBSTRATE
OATP-8
TRANSPORTER -> INHIBITOR
IC50
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
OATP1B1
TRANSPORTER -> SUBSTRATE
IC50
BSEP
TRANSPORTER -> SUBSTRATE
IC50
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
inhibit 6.7% at 10 μM
IC50
Related Record Type Details
Structure of DES-(METHYLCYCLOPROPYLSULFONAMIDE)-VOXILAPREVIR
METABOLITE -> PARENT
FECAL
Structure of 17-DESMETHYL VOXILAPREVIR
METABOLITE -> PARENT
FECAL
Related Record Type Details
Structure of VOXILAPREVIR
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
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HHS VULNERABILITY DISCLOSURE
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