Daclatasvir

SKU: orb1300958

Description

Daclatasvir (BMS-790052) is a potent and selective HCV NS5A inhibitor, demonstrating picomolar EC50 activity against multiple HCV genotypes in replicon assays and the infectious JFH-1 virus. Its efficacy, validated in both in vitro studies and pivotal Phase 3 clinical trials, makes it a critical tool for antiviral research targeting hepatitis C.

Research Area

Infectious Disease & Virology, Pharmacology & Drug Discovery, Protein Biochemistry

Key Properties

• CAS Number: 1009119-64-5
• MW: 738.88
• Purity: 99.99% (May vary between batches)
• Formula: C₄₀H₅₀N₈O₆
• SMILES: COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1c1ncc([nH]1)-c1ccc(cc1)-c1ccc(cc1)-c1cnc([nH]1)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C
• Target: HCV Protease
• Solubility: DMSO:136 mg/mL (184.06 mM);Ethanol:136 mg/mL (184.06 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (5.41 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  HCV NS5A:9 pM-50 pM(EC50)
• In Vivo:
  In a randomized, double-blind, placebo-controlled, single ascending-dose study, Daclatasvir (BMS-790052) is administered at six dose levels to healthy, non-HCV-infected subjects over a range of 1 to 200 mg as an oral solution. Daclatasvir is safe and well tolerated up to 200 mg with no clinically relevant adverse effects. After oral administration, Daclatasvir is readily absorbed, with dose-proportional exposures over the studied dose range, and all subjects have drug concentrations greater than the protein-binding-adjusted EC90 for genotypes 1a and 1b, as measured in the replicon assay, at and beyond 24 h post-dose. (The protein binding-adjusted EC90 figures are derived from an analysis of the effect of the addition of human serum on antiviral activity in replicons. In the presence of 40% human serum, the EC90 for Daclatasvir is 383 pM (0.28 ng/mL) for the genotype 1a replicon and 49 pM (0.04 ng/mL) for the genotyope 1b replicon). Mice in each group that developed persistent HCV infection are divided into two treatment groups. One group receive 4 weeks of Asunaprevir/Daclatasvir treatment and the other group received 4 weeks of Ledipasvir/GS-558093 treatment. Asunaprevir/Daclatasvir therapy and Ledipasvir/GS-558093 therapy rapidly decease serum HCV RNA levels to below the sensitivity, and they are not detected after completion of the therapy except for two mice in the Ledipasvir/GS-558093 group.
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• In Vitro:
  Daclatasvir is one of the most potent inhibitors of HCV replication reported so far. The mean EC50 valuses of Daclatasvir are 50 and 9pM for HCV genotype 1a and 1b replicons, respectively. Daclatasvir 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 10μM. This confirms Daclatasvir's specificity for HCV. In Huh7 cells harboring the HCV genotype 1b replicons, Daclatasvir blocks both transient and stable HCV genome replication, with EC50 values raging from 1-15 pM. Daclatasvir (100 pM or 1 nM) has been shown to alter the subcellular localization and biochemical fractionation of NS5A. Daclatasvir inhibits hybrid replicons containing HCV genotype-4 NS5A genes with EC50 of 7-13 pM. Residue 30 of NS5A is an important site for Daclatasvir-mediated resistance in the hybrid replicons.
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• Cell Research:
  BMS-790052 is added to 96-well plates containing HCV replicon cells seeded approximately 12 hours before in 200 μL media.The cell plates are tested for replication activity and cytotoxicity after 72 hours of incubation. Cytotoxicity is measured with CellTiter-Blue, after which the media and dye are removed, plates are inverted and the remaining liquid is blotted with paper towels. Replication activity of the HCV genotype 1a cell lines is quantified using Renilla luciferase. 1× Renilla luciferase lysis buffer (30 μL) is added to each well and plates are incubated with gentle shaking for 15 min. Renilla luciferase substrate (40 μL) is then added and the signals are detected using a Top Count luminometer set for light emission quantification. One hundred per cent activity is calculated for each cell line for the DMSO-only wells; percentage activity is calculated for each concentration of the inhibitor by dividing the average value for wells containing compound by the average value for wells containing DMSO.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Daklinza, Daclatasvir, EBP 883, EBP883, EBP-883, antiviral, BMS790052, BMS-790052, BMS 790052, genotypes, Inhibitor, HCV Protease, HCVProtease, HCV, HCV NS5A, Hepatitis C virus, OATP1B1, OATP1B3, inhibit, NS5A, JFH-1, replicon

Compound Identifiers

PubChem CID

25154714