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

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

1437696000000
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
experiment_type: multiple
dose_type: Highest studied dose
co-adm with
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/21837752
    unhealthy, 44 years (range: 34-49 years)
    population: unhealthy
    age: 44 years (range: 34-49 years)
    sex: M+F
    food_status:
    n:
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/21837752
    Other AEs: Headache, Diarrhea...
    Other AEs:
    Headache (25%)
    Diarrhea (25%)
    Abdominal pain (25%)

    data_source:
    https://pubmed.ncbi.nlm.nih.gov/21837752
    200 mg single, oral
    Highest studied dose
    dose: 200 mg
    route: oral
    experiment_type: single
    dose_type: Highest studied dose
    co-adm with
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/21837752
      healthy, adult
      population: healthy
      age: adult
      sex:
      food_status:
      n:
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/21837752
      AEs

      AEs

      AESignificanceDosePopulation
      Abdominal pain 25%
      100 mg 1 times / day multiple, oral
      Highest studied dose
      dose: 100 mg 1 times / day
      route: oral
      experiment_type: multiple
      dose_type: Highest studied dose
      co-adm with
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/21837752
        unhealthy, 44 years (range: 34-49 years)
        population:
        age:
        sex:
        food_status:
        n:
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/21837752
        Diarrhea 25%
        100 mg 1 times / day multiple, oral
        Highest studied dose
        dose: 100 mg 1 times / day
        route: oral
        experiment_type: multiple
        dose_type: Highest studied dose
        co-adm with
          data_source:
          https://pubmed.ncbi.nlm.nih.gov/21837752
          unhealthy, 44 years (range: 34-49 years)
          population:
          age:
          sex:
          food_status:
          n:
          data_source:
          https://pubmed.ncbi.nlm.nih.gov/21837752
          Headache 25%
          100 mg 1 times / day multiple, oral
          Highest studied dose
          dose: 100 mg 1 times / day
          route: oral
          experiment_type: multiple
          dose_type: Highest studied dose
          co-adm with
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/21837752
            unhealthy, 44 years (range: 34-49 years)
            population:
            age:
            sex:
            food_status:
            n:
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/21837752
            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
            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
            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
            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
            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
            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
            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
            Tox targets

            Tox targets

            PubMed

            PubMed

            TitleDatePubMed
            Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect.
            2010 May 6
            Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system.
            2010 Sep
            Colony-forming assays reveal enhanced suppression of hepatitis C virus replication using combinations of direct-acting antivirals.
            2011 Jun
            Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.
            2011 Sep
            Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics.
            2012 Apr 15
            In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A.
            2012 Mar
            Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors.
            2012 May 15
            Synthesis and evaluation of non-dimeric HCV NS5A inhibitors.
            2013 Apr 1
            In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.
            2013 Nov
            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
            Pharmacological disruption of hepatitis C NS5A protein intra- and intermolecular conformations.
            2014 Feb
            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