VOXILAPREVIR

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 Search

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

Description
Sources: https://www.drugbank.ca/drugs/DB12026 | https://www.ncbi.nlm.nih.gov/pubmed/29115151 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209195Orig1s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/29063860

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

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus serine protease, NS3/NS4A 13 Target ID: CHEMBL2095231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29175627 \| https://www.drugbank.ca/drugs/DB12026 \| https://www.ncbi.nlm.nih.gov/pubmed/29063860	Inhibitor 8297		38.0 pM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: https://www.drugs.com/history/vosevi.html	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

C_max

Value	Dose	Analyte	Population
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

Value	Dose	Analyte	Population
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

T_1/2

Value	Dose	Analyte	Population
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
IFNL4 Genotype Is Associated With Virologic Relapse After 8-Week Treatment With Sofosbuvir, Velpatasvir, and Voxilaprevir.	2017 Dec	29107709
Betrixaban, sofosbuvir/velpatasvir/voxilaprevir, and glecaprevir/pibrentasvir.	2017 Nov-Dec	29092766
Characterization of HCV resistance from a 3-day monotherapy study of voxilaprevir, a novel pangenotypic NS3/4A protease inhibitor.	2018	29063860
Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C.	2018 Apr	29115151

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.

Name

Type

Language

VOXILAPREVIR

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