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    Daclatasvir (BMS790052; EBP883)
    Daclatasvir (BMS790052; EBP883)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0724
    CAS #: 1009119-64-5 (free base)Purity ≥98%

    Description: Daclatasvir (formerly BMS-790052; EBP-883; trade name Daklinza), a direct-acting antiviral agent, is a selective inhibitor of HCV NS5A (nonstructural protein) with an EC50 of 9-50 pM. Daclatasvir has been used in combination with another antiviral drug (sofosbuvir) for the treatment of hepatitis C (HCV) by causing a decrease in serum HCV RNA levels. It is was developed by BMS and was approved in EU in 2014. Daclatasvir inhibits the HCV nonstructural protein NS5A. Recent study suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA. Daclatasvir has been tested in combination regimens with pegylated interferon and ribavirin, as well as with other direct-acting antiviral agents including asunaprevir and sofosbuvir.

    References: Nature. 2010 May 6;465(7294):96-100; Virology. 2011 May 25;414(1):10-8; Antimicrob Agents Chemother. 2012 Mar;56(3):1588-90. 

    Related CAS: 1009119-64-5 (free base); 1009119-65-6 (Di-HCl)

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    Molecular Weight (MW)738.88
    CAS No.1009119-64-5 (free base); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 148 mg/mL (200.3 mM)
    Water: <1 mg/mL
    Ethanol: 148 mg/mL (200.3 mM)
    SMILES CodeO=C(N1CCC[[email protected]]1C2=NC=C(C3=CC=C(C4=CC=C(C=C4)C5=CN=C(N5)[[email protected]@H]6CCCN6C([[email protected]](C(C)C)NC(OC)=O)=O)C=C3)N2)[[email protected]](C(C)C)NC(OC)=O
    SynonymsBMS-790052; Daclatasvir; BMS790052; BMS 790052; EBP883; EBP 883; EBP-883; Daklinza (trade name) 

    Chemical Name: 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


    InChi Code: InChI=1S/C40H50N8O6/c1-23(2)33(37(49)45-39(51)53-5)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)34(24(3)4)38(50)46-40(52)54-6/h11-18,21-24,31-34H,7-10,19-20H2,1-6H3,(H,41,43)(H,42,44)(H,45,49,51)(H,46,50,52)/t31-,32-,33-,34-/m0/s1

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    In Vitro

    In vitro activity: BMS-790052 is one of the most potent inhibitors of HCV replication reported so far. The mean EC50 valuses of BMS-790052 are 50 and 9 pM for HCV genotype 1a and 1b replicons, respectively. BMS-790052 displays a therapeutic index (CC50/EC50) of at least 105 and is inactive towards a panel of 10 RNA and DNA viruses, with EC50 higher than 10 μM. This confirms BMS-790052's specificity for HCV. In Huh7 cells harboring the HCV genotype 1b replicons, BMS-790052 blocks both transient and stable HCV genome replication, with EC50 values raging from 1-15 pM. BMS-790052 (100 pM or 1 nM) has been shown to alter the subcellular localization and biochemical fractionation of NS5A. BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with EC50 of 7-13 pM. Residue 30 of NS5A is an important site for BMS-790052-mediated resistance in the hybrid replicons.

    Kinase Assay: Daclatasvir is a potent HCV NS5A protein inhibitor, with mean EC50 values of 50 and 9 pM against genotype 1a and 1b replicons, respectively.

    Cell Assay: The antiviral activity of daclatasvir towards genotypes was assessed by using replication-competent 1a or 1b replicons to construct hybrids in which the entire NS5A coding region or the first 100 amino acids of NS5A from different genotypes replaced the corresponding sequence of the parent replicon. Daclatasvir was reported to be highly potent across all HCV genotypes with half-maximum effective concentrations (EC50) ranging from 9 to 146 pM

    In VivoHumanized liver chimeric mice, whose chimeric rate of the liver is estimated as over 40 %, are injected intravenously with 100 µL of HCV-positive human serum samples. After inoculation, their blood is collected from an external jugular vein every 1-4 weeks. The HCV RNA levels are measured by the COBAS TaqMan HCV test in 100-fold diluted serum with a lower measurement range of 3.2 log IU/mL serum. After serum levels of HCV RNA reach plateau levels, mice are administered orally once a day for 4 weeks with one of the following: 40 mg/kg of Asunaprevir plus 30 mg/kg of Daclatasvir, 15 mg/kg of Ledipasvir plus 50 mg/kg of GS-558093 and 50 mg/kg of GS-558093 plus 400 mg/kg of Telaprevir.
    Animal modelMice
    Formulation & Dosage30 mg/kg; oral
    ReferencesNature. 2010 May 6;465(7294):96-100; Virology. 2011 May 25;414(1):10-8; Antimicrob Agents Chemother. 2012 Mar;56(3):1588-90. 

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Daclatasvir (BMS-790052)

    BMS-790052 alters the subcellular fractionation patterns of NS proteins. Virology. 2011 May 25;414(1):10-8.

    Daclatasvir (BMS-790052)

    BMS-790052 alters the subcellular localization of NS viral proteins. Virology. 2011 May 25;414(1):10-8.

    Daclatasvir (BMS-790052)

    BMS-790052 blocks HCV genome replication. Virology. 2011 May 25;414(1):10-8.

    Daclatasvir (BMS-790052)

    Reversal of BMS-790052-induced alterations on subcellular localization of NS proteins expressed from a replicon containing the BMS-790052-resistant mutation (Y93H) in NS5A. Virology. 2011 May 25;414(1):10-8.

    Daclatasvir (BMS-790052)

    BMS-790052 affects neither the in vitro replicase activity of pre-assembled RCs nor the self-dimerization of NS5A proteins. Virology. 2011 May 25;414(1):10-8.


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