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

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H50N8O6
Molecular Weight 738.8765
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DACLATASVIR

SMILES

CC(C)[C@@]([H])(C(=O)N1CCC[C@@]1([H])c2ncc(-c3ccc(cc3)-c4ccc(cc4)-c5cnc([C@]6([H])CCCN6C(=O)[C@]([H])(C(C)C)N=C(O)OC)[nH]5)[nH]2)N=C(O)OC

InChI

InChIKey=FKRSSPOQAMALKA-CUPIEXAXSA-N
InChI=1S/C40H50N8O6/c1-23(2)33(45-39(51)53-5)37(49)47-19-7-9-31(47)35-41-21-29(43-35)27-15-11-25(12-16-27)26-13-17-28(18-14-26)30-22-42-36(44-30)32-10-8-20-48(32)38(50)34(24(3)4)46-40(52)54-6/h11-18,21-24,31-34H,7-10,19-20H2,1-6H3,(H,41,43)(H,42,44)(H,45,51)(H,46,52)/t31-,32-,33-,34-/m0/s1

HIDE SMILES / InChI
Daclatasvir (BMS-790052) is a direct-acting antiviral agent against Hepatitis C Virus (HCV) used for the treatment of chronic HCV genotype 3 infection. Daclatasvir prevents RNA replication and virion assembly by binding to NS5A, a nonstructural phosphoprotein encoded by HCV. Binding to the N-terminus of the D1 domain of NS5A prevents its interaction with host cell proteins and membranes required for virion replication complex assembly.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DAKLINZA

Approved Use

DAKLINZA is indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection [see Dosage and Administration (2) and Clinical Studies (14)

Launch Date

1.437696E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1295 ng/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1582 ng/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
291 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
257 ng/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
610 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
734 ng/mL
30 mg 1 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
148 ng/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1226 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
16.4 ng/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2816 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
11475 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
15666 ng × h/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2371 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2453 ng × h/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4548 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6275 ng × h/mL
30 mg 1 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9680 ng × h/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
13471 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
162 ng × h/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
31793 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.5 h
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
13.5 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9.83 h
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
11 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACLATASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 44 years (range: 34-49 years)
n = 4
Health Status: unhealthy
Condition: HCV infection
Age Group: 44 years (range: 34-49 years)
Sex: M+F
Population Size: 4
Sources:
Other AEs: Headache, Diarrhea...
Other AEs:
Headache (25%)
Diarrhea (25%)
Abdominal pain (25%)
Sources:
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 25%
100 mg 1 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 44 years (range: 34-49 years)
n = 4
Health Status: unhealthy
Condition: HCV infection
Age Group: 44 years (range: 34-49 years)
Sex: M+F
Population Size: 4
Sources:
Diarrhea 25%
100 mg 1 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 44 years (range: 34-49 years)
n = 4
Health Status: unhealthy
Condition: HCV infection
Age Group: 44 years (range: 34-49 years)
Sex: M+F
Population Size: 4
Sources:
Headache 25%
100 mg 1 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 44 years (range: 34-49 years)
n = 4
Health Status: unhealthy
Condition: HCV infection
Age Group: 44 years (range: 34-49 years)
Sex: M+F
Population Size: 4
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no
no
no
yes
yes
unlikely (co-administration study)
Comment: interaction between steady-state DCV and single-dose midazolam (a sensitive CYP3A4 probe) demonstrated that DCV is unlikely to impact the exposure of concomitant medications through CYP3A4-related mechanisms; midazolam exposure was minimally decreased (13%) during co-administration
Page: 132.0
yes
unlikely (co-administration study)
Comment: interaction between steady-state DCV and single-dose midazolam (a sensitive CYP3A4 probe) demonstrated that DCV is unlikely to impact the exposure of concomitant medications through CYP3A4-related mechanisms; midazolam exposure was minimally decreased (13%) during co-administration
Page: 132.0
yes
weak (co-administration study)
Comment: The co-administration of DCV with digoxin, both agents at steady-state, resulted in a 27% increase in digoxin AUC during co-administration
Page: 13.0
yes
yes (co-administration study)
Comment: co-administration with DCV at steady-state, single-dose rosuvastatin exposure was increased (C max, two-fold; AUC, 58% increase
Page: 13.0
yes
yes (co-administration study)
Comment: co-administration with DCV at steady-state, single-dose rosuvastatin exposure was increased (C max, two-fold; AUC, 58% increase
Page: 13.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
likely (co-administration study)
Comment: coadministration with CYP3A4 inhibitors/inducers are likely to affect drug concentration
Page: 132.0
yes
no (co-administration study)
Comment: cyclosporine, which inhibits multiple transporters including P-gp, did not have a clinically relevant effect on the pharmacokinetics of daclatasvir
Page: 13.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system.
2010 Sep
Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.
2011 Sep
In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A.
2012 Mar
Characterizations of HCV NS5A replication complex inhibitors.
2013 Sep
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.
2014
The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance.
2014 Jun
Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.
2014 Mar 13
Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir.
2014 Mar 13
Changing the face of hepatitis C management - the design and development of sofosbuvir.
2015
Interferon-free therapy for hepatitis C: The hurdles amid a golden era.
2015 Sep
Patents

Sample Use Guides

The recommended dosage is 60 mg, taken orally, once daily in combination with sofosbuvir for 12 weeks. Drug may be taken with or without food.
Route of Administration: Oral
Daclatasvir had a median EC50 value of 0.2 nM against hybrid replicons containing genotype 3a subject-derived NS5A sequences without detectable daclatasvir resistance-associated polymorphisms at NS5A amino acid positions 28, 30, 31, or 93 with a median EC50 value of 13.5 nM (range, 1.3-50 nM). Similarly, the EC50 values of daclatasvir against 3 genotype 3b and 1 genotype 3i subject-derived NS5A sequences with polymorphisms (relative to a genotype 3a reference) at positions 30 or 31 were ≥3620 nM. The median EC50 values of daclatasvir for genotypes 1a, 1b, 2, 4, and 5 subject-derived NS5A hybrid replicons were 0.008 nM (range, 0.002-2409 nM, n=40), 0.002 nM (range, 0.0007-10 nM, n=42), 16 nM (range, 0.005-60 nM, n=16), 0.025 nM (range, 0.001-158 nM, n=14), and 0.004 nM (range, 0.003-0.019 nM, n=3), respectively. The EC50 value against a single HCV genotype 6 derived replicon was 0.054 nM.
Name Type Language
DACLATASVIR
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
DIMETHYL N,N'-((1,1'-BIPHENYL)-4,4'-DIYLBIS(1H-IMIDAZOLE-5,2-DIYL-((2S)-PYRROLIDINE-2,1-DIYL)((1S)-3-METHYL-1-OXOBUTANE-1,2-DIYL)))DICARBAMATE
Common Name English
DACLATASVIR [USAN]
Common Name English
EBP-883
Code English
BMS 790052
Code English
DACLATASVIR [INN]
Common Name English
DACLATASVIR [MI]
Common Name English
EBP 883
Code English
CARBAMIC ACID, N,N'-((1,1'-BIPHENYL)-4,4'-DIYLBIS(1H-IMIDAZOLE-5,2-DIYL-(2S)-2,1-PYRROLIDINEDIYL((1S)-1-(1-METHYLETHYL)-2-OXO-2,1-ETHANEDIYL)))BIS-, C,C'-DIMETHYL ESTER
Common Name English
DACLATASVIR [WHO-DD]
Common Name English
DCV
Common Name English
BMS-790052
Code English
Classification Tree Code System Code
WHO-ATC J05AP07
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
WHO-ATC J05AX14
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
NCI_THESAURUS C281
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
NDF-RT N0000191256
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
Code System Code Type Description
NDF-RT
N0000185503
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
NDF-RT
N0000190113
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
LACTMED
Daclatasvir
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
EVMPD
SUB75341
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
CAS
1009119-64-5
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
NDF-RT
N0000190108
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 1B3 Inhibitors [MoA]
DRUG BANK
DB09102
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
RXCUI
1606218
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY RxNorm
MESH
C549273
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
INN
9483
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
MERCK INDEX
M11764
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
DRUG CENTRAL
4875
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
FDA UNII
LI2427F9CI
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
NCI_THESAURUS
C114981
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
PUBCHEM
25154714
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
NDF-RT
N0000190107
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
ChEMBL
CHEMBL2023898
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY
WIKIPEDIA
Daclatasvir
Created by admin on Sat Jun 26 13:28:14 UTC 2021 , Edited by admin on Sat Jun 26 13:28:14 UTC 2021
PRIMARY