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

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H50N8O6.2ClH
Molecular Weight 811.797
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DACLATASVIR DIHYDROCHLORIDE

SMILES

Cl.Cl.COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)[C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C

InChI

InChIKey=BVZLLUDATICXCI-JMSCDMLISA-N
InChI=1S/C40H50N8O6.2ClH/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);2*1H/t31-,32-,33-,34-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula C40H50N8O6
Molecular Weight 738.875
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

2015
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
Synthesis and evaluation of non-dimeric HCV NS5A inhibitors.
2013 Apr 1
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.
2014
Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir.
2014 Mar 13
Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.
2014 Mar 13
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 20:15:01 GMT 2023
Edited
by admin
on Fri Dec 15 20:15:01 GMT 2023
Record UNII
50ZO25C11D
Record Status Validated (UNII)
Record Version
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Name Type Language
DACLATASVIR DIHYDROCHLORIDE
USAN   WHO-DD  
USAN  
Official Name 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, HYDROCHLORIDE (1:2)
Common Name English
METHYL N-((2S)-1-((2S)-2-(5-(4-(4'-(2-((2S)-1-((2S)-2-(METHOXYCARBONYLAMINO)-3-METHYLBUTANOYL)PYRROLIDIN-2-YL)-1H-IMIDAZOL-5-YL)PHENYL)PHENYL)-1H-IMIDAZOL-2-YL)PYRROLIDIN-1-YL)-3-METHYL-1-OXOBUTAN-2-YL)CARBAMATE DIHYDROCHLORIDE
Common Name English
DACLATASVIR DIHYDROCHLORIDE [ORANGE BOOK]
Common Name English
DAKLINZA
Brand Name English
Daclatasvir dihydrochloride [WHO-DD]
Common Name English
DIMETHYL N,N'-(BIPHENYL-4,4'-DIYLBIS(1H-IMIDAZOLE-5,2-DIYL-((2S)-PYRROLIDINE-2,1- DIYL)((1S)-1-(1-METHYLETHYL)-2-OXOETHANE-2,1-DIYL)))DICARBAMATE DIHYDROCHLORIDE
Common Name English
BMS-790052-05
Code English
DACLATASVIR HYDROCHLORIDE
JAN  
Official Name English
DACLATASVIR DIHYDROCHLORIDE [USAN]
Common Name English
DACLATASVIR DIHYDROCHLORIDE [MI]
Common Name English
DACLATASVIR HYDROCHLORIDE [JAN]
Common Name English
BMS 790052-05
Code English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS DAKLINZA (AUTHORIZED: HEPATITIS C, CHRONIC)
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
Code System Code Type Description
USAN
XX-59
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
CHEBI
83800
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
JAPANESE REVIEW
DAKLINZA
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY APPROVED JULY 2014
FDA UNII
50ZO25C11D
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
SMS_ID
100000156586
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
CAS
1009119-65-6
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
DRUG BANK
DBSALT001166
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
EPA CompTox
DTXSID201027744
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
ChEMBL
CHEMBL2023898
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
NCI_THESAURUS
C166798
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
PUBCHEM
25154713
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
MERCK INDEX
m11764
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
RXCUI
1606217
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY RxNorm
EVMPD
SUB130532
Created by admin on Fri Dec 15 20:15:01 GMT 2023 , Edited by admin on Fri Dec 15 20:15:01 GMT 2023
PRIMARY
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