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

Details

Stereochemistry ABSOLUTE
Molecular Formula C49H54N8O8
Molecular Weight 883.0037
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VELPATASVIR

SMILES

CC(C)[C@@]([H])(C(=O)N1[C@@]([H])(C)CC[C@@]1([H])c2nc3ccc4cc5-c6ccc(cc6COc5cc4c3[nH]2)-c7cnc([C@]8([H])C[C@@]([H])(CN8C(=O)[C@@]([H])(c9ccccc9)N=C(O)OC)COC)[nH]7)N=C(O)OC

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 883.0037
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
28.3 ng/mL
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
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
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
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
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
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
172 ng × h/mL
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
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
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
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
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
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
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
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.7 h
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
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
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
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
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
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
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
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
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
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.3%
unknown, unknown
VELPATASVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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:
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:
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:
AEs

AEs

AESignificanceDosePopulation
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
PubMed

PubMed

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

Sample Use Guides

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
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 Jun 26 13:35:18 UTC 2021
Edited
by admin
on Sat Jun 26 13:35:18 UTC 2021
Record UNII
KCU0C7RS7Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VELPATASVIR
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
VELPATASVIR [MI]
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
FDA ORPHAN DRUG 554816
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
NCI_THESAURUS C281
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
WHO-ATC J05AP56
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
NDF-RT N0000191256
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
NCI_THESAURUS C783
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
WHO-ATC J05AP55
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
Code System Code Type Description
LACTMED
Velpatasvir
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
NDF-RT
N0000190107
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
DRUG CENTRAL
5154
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
FDA UNII
KCU0C7RS7Z
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
NDF-RT
N0000190108
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 1B3 Inhibitors [MoA]
CAS
1377049-84-7
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545062
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
NDF-RT
N0000190113
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
RXCUI
1799206
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
NDF-RT
N0000190109
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 2B1 Inhibitors [MoA]
NDF-RT
N0000185503
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
MERCK INDEX
M11941
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
PUBCHEM
67683363
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
NCI_THESAURUS
C152851
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
INN
9960
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
DRUG BANK
DB11613
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
EVMPD
SUB180213
Created by admin on Sat Jun 26 13:35:18 UTC 2021 , Edited by admin on Sat Jun 26 13:35:18 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
inhibit 30% at 10 ?M
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
TRANSPORTER -> SUBSTRATE
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC