VELPATASVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C49H54N8O8
Molecular Weight	883.0019
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC[C@H]1C[C@H](N(C1)C(=O)[C@H](NC(=O)OC)C2=CC=CC=C2)C3=NC=C(N3)C4=CC=C5C(COC6=CC7=C(C=CC8=C7NC(=N8)[C@@H]9CC[C@H](C)N9C(=O)[C@@H](NC(=O)OC)C(C)C)C=C56)=C4

InChI

InChIKey=FHCUMDQMBHQXKK-CDIODLITSA-N

InChI=1S/C49H54N8O8/c1-26(2)41(54-48(60)63-5)47(59)57-27(3)12-17-38(57)45-51-36-16-14-30-20-35-33-15-13-31(19-32(33)25-65-40(35)21-34(30)43(36)53-45)37-22-50-44(52-37)39-18-28(24-62-4)23-56(39)46(58)42(55-49(61)64-6)29-10-8-7-9-11-29/h7-11,13-16,19-22,26-28,38-39,41-42H,12,17-18,23-25H2,1-6H3,(H,50,52)(H,51,53)(H,54,60)(H,55,61)/t27-,28-,38-,39-,41-,42+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C49H54N8O8
Molecular Weight	883.0019
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28193657 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27730529

Velpatasvir (VEL; GS-5816) is an inhibitor of HCV NS5A protein, it demonstrated favourable in vitro and in vivo properties, including potent antiviral activity against hepatitis C virus genotypes 1 to 6 replicon, good metabolic stability, low systemic clearance, and adequate bioavailability and physicochemical properties to warrant clinical evaluation. Velpatasvir is used together with sofosbuvir in the treatment of hepatitis C infection of all six major genotypes. A once-daily, single-tablet, pangenotypic regimen comprising the HCV NS5B polymerase inhibitor sofosbuvir and the HCV NS5A inhibitor velpatasvir (sofosbuvir/ velpatasvir; Epclusa) has recently been approved for the treatment of adults with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in the USA, EU and Canada.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nonstructural protein 5A 11 Target ID: CHEMBL3307224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27730529 \| http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf	Inhibitor 8297		0.014 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42 Sources: http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf https://www.ncbi.nlm.nih.gov/pubmed/27730529	Primary		Approved 8429	Epclusa Approved Use EPCLUSA is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor, and is indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection. Launch Date 1.46707199E12

C_max

Value	Dose	Analyte	Population
28.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
411 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
669 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1200 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
22.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
371 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
398 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
608 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
575 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
800 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: LOW-FAT
1120 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
172 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3030 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4890 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9510 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
159 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3020 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3620 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
4980 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5060 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7120 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: LOW-FAT
9580 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
13.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
15.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
16.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
15.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
16.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: LOW-FAT
15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	VELPATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.3% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28193657	unknown, unknown		VELPATASVIR plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	Disc. AE: Nausea... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Nausea (3.2%) Other AEs: Headache (12.9%) Nausea (6.5%) Vomiting (6.5%) Cough (3.2%) Hypertension (3.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/26183611

AEs

AE	Significance	Dose	Population
Headache	12.9%	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611
Cough	3.2%	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611
Hypertension	3.2%	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611
Nausea	3.2% Disc. AE	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611
Nausea	6.5%	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611
Vomiting	6.5%	150 mg 1 times / day multiple, oral Highest studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26183611	unhealthy, 49 years (range: 28–63 years) n = 31 Health Status: unhealthy Condition: genotype 1–4 hepatitis C virus Age Group: 49 years (range: 28–63 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/26183611

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:133009	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:133009
ChemicalBook	CB62743053	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62743053
MolPort	MolPort-044-561-847	https://www.molport.com/shop/molecule-link/MolPort-044-561-847
MolPort	MolPort-046-423-233	https://www.molport.com/shop/molecule-link/MolPort-046-423-233
ZINC	ZINC000203686879	http://zinc15.docking.org/substances/ZINC000203686879

PubMed

Title	Date	PubMed
Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C.	2016 Oct	27730529
Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects.	2017 May	28193657

Patents

Sample Use Guides

In Vivo Use Guide

Recommended dosage: One tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily with or without food

Route of Administration: Oral

In Vitro Use Guide

Velpatasvir had mean EC50 values of 0.014, 0.016, 0.005–0.016, 0.002–0.006, 0.004, 0.009, 0.004, 0.021–0.054, 0.006–0.009 and 0.130 nmol/L against laboratory replicons with HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, 6a and 6e, respectively, and median EC50 values of 0.002–0.024 nmol/L against replicons containing NS5A from clinical isolates with HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 4r, 5a, 6a and 6e.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:45:18 UTC 2023` Edited by `admin` on `Sat Dec 16 09:45:18 UTC 2023`
Record UNII	KCU0C7RS7Z
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VELPATASVIR

Official Name

English

VELPATASVIR [MI]

Common Name

English

VELPATASVIR [JAN]

Common Name

English

velpatasvir [INN]

Common Name

English

Velpatasvir [WHO-DD]

Common Name

English

EPCLUSA COMPONENT VELPATASVIR

Brand Name

English

VELPATASVIR COMPONENT OF EPCLUSA

Brand Name

English

VELPATASVIR [USAN]

Common Name

English

VOSEVI COMPONENT VELPATASVIR

Common Name

English

VELPATASVIR COMPONENT OF VOSEVI

Common Name

English

VELPATASVIR [ORANGE BOOK]

Common Name

English

GS-5816

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C281