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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

CC[C@@H]1[C@@H]2CN([C@@H]1C(=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=C(O2)N=C7C=C(OC)C=CC7=N6)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
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

Targets

Targets

Primary TargetPharmacologyConditionPotency
38.0 pM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VOSEVI
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
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 Mon Oct 21 19:46:05 UTC 2019
Edited
by admin
on Mon Oct 21 19:46:05 UTC 2019
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 COMPONENT OF VOSEVI
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 Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
NDF-RT N0000182639
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
NCI_THESAURUS C281
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
WHO-ATC J05AP56
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C152922
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
RXCUI
1939323
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
CAS
1535212-07-7
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
INN
10143
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
ChEMBL
CHEMBL3707372
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
EVMPD
SUB185303
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
PRIMARY
PUBCHEM
89921642
Created by admin on Mon Oct 21 19:46:05 UTC 2019 , Edited by admin on Mon Oct 21 19:46:05 UTC 2019
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
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC