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

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
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 1.50024959E12

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
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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:39:01 UTC 2023` Edited by `admin` on `Sat Dec 16 09:39:01 UTC 2023`
Record UNII	0570F37359
Record Status	`Validated (UNII)`
Record Version

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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