Daclatasvir (BMS-790052)

Catalog No.S1482 Batch:S148202

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Technical Data

Formula

C40H50N8O6
Molecular Weight 738.88 CAS No. 1009119-64-5
Solubility (25°C)* In vitro DMSO 148 mg/mL (200.3 mM)
Ethanol 148 mg/mL (200.3 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Daclatasvir (BMS-790052, EBP883) is a highly selective inhibitor of HCV NS5A with EC50 of 9-50 pM, for a broad range of HCV replicon genotypes and the JFH-1 genotype 2a infectious virus in cell culture. Phase 3.
Targets
HCV NS5A [1]
9 pM-50 pM(EC50)
In vitro Daclatasvir (BMS-790052) is one of the most potent inhibitors of HCV replication reported so far. The mean EC50 values of this compound are 50 and 9 pM for HCV genotype 1a and 1b replicons, respectively. It 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 its specificity for HCV. [1] In Huh7 cells harboring the HCV genotype 1b replicons, it blocks both transient and stable HCV genome replication, with EC50 values ranging from 1-15 pM. This compound (100 pM or 1 nM) has been shown to alter the subcellular localization and biochemical fractionation of NS5A. [2] It 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. [3]
Features First-in-class, highly selective inhibitor of hepatitis C virus (HCV) NS5A with picomolar EC50 values.

Protocol (from reference)

Kinase Assay:[4]
  • FRET assay for HCV NS5A inhibitors

    该肽（Ac-Asp-Glu-Asp [EDANS]-Glu-Glu-Abu-[COO] Ala-Ser-Lys [DABCYL]-NH2）在一端附近含有荧光供体{EDANS，5-[（2-氨基乙基）氨基]萘-1-磺酸}，另一端附近含有受体{DABCYL，4-[（4-二甲基氨基）苯基]偶氮}苯甲酸}。供体和受体之间的分子间共振能量转移会猝灭该肽的荧光，但随着NS3蛋白酶切割该肽，产物从共振能量转移猝灭中释放出来。随着更多底物被NS3蛋白酶切割，供体的荧光随时间增强。检测试剂为：5×荧光素酶细胞培养裂解试剂用dH2O稀释至1×，NaCl（150 mM），FRET肽（20 μM）。将HCV-Huh-7细胞置于96孔板中，并使其附着过夜（每孔1×104个细胞）。第二天，将Daclatasvir (BMS-790052)加入孔中，并将板孵育72小时。然后用PBS冲洗板，并通过每孔加入30 μL上述FRET肽检测试剂用于FRET检测。使用Cytofluor 4000仪器获取信号，该仪器设置为340 nm（激发）/490 nm（发射）自动模式，运行20个循环或更少，并在动力学模式下读取板。FRET后，每孔加入40 μL荧光素酶底物，并测量荧光素酶活性。
Cell Assay:[1]
  • Cell lines

    HCV replicon cells (Huh7)

  • Concentrations

    0.1 pM - 50 μM, dissolved in DMSO (the final concentration of DMSO is 0.5%)

  • Incubation Time

    72 hours

  • Method

    Daclatasvir (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 this compound by dividing the average value for wells containing it by the average value for wells containing DMSO.

References

  • https://pubmed.ncbi.nlm.nih.gov/20410884/
  • https://pubmed.ncbi.nlm.nih.gov/21513964/
  • https://pubmed.ncbi.nlm.nih.gov/22203595/
  • https://pubmed.ncbi.nlm.nih.gov/15793110/

Customer Product Validation

<p>The toxicity of BMS-790052 (BMS) and Telaprevir (TPV) was measured by seeding 96-well plates to 70% confluence and exposing the cells to up to 50 μM of compound for 72 hours. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was added to each well at a final concentration of 500 μg/ml 4 h before dissolving crystals in 100 μl of DMSO and measuring at 550 nm UV wavelengths. The 50% cytotoxic concentration (CC50) was then calculation using the OD550 value and the following formula: log CC50=log concentration of HPP-[(HPP-50)/(HPP-LPP)×log d HPP: highest protective percentage closest to 50% LPP: Lowest protective percentage closest to 50% d: dilution factor</p>

, 2011 , Dr. Julie Sheldon,Dr Esteban Domingo and Dr Celia Perales

<p>Huh7.5 cells were infected with JFH-1 (2a) strain. Once the cells reached 80% infectivity they were treated with pMconcentration of BMS790052 for two different time points. Cells were collected in SDS sample loading buffer and probed for NS5A and GAPDH. After 16hrs hyperphosphorylated NS5A disappeared with increasing concentration of the drug. 40hrs of treatment resulted complete disappearance of NS5A. GAPDH is internal control.</p><div><div> </div></div><p> </p>

, 2011 , Dr. Anita Nag of Florida State University

<p>80% infected HCV JFH-1 cells were treated with several concentrations of BMS790052 in pMrange. Cells were fixed after 16hrs and NS5A was probed.Cells treated with BMS790052 shows NS5A present in clusters compared to an even cytoplasmic distribution in untreated cells.</p>

, 2011 , Dr. Anita Nag of Florida State University

Sensitivity of PR63cc to the combinatory treatment with asunaprevir and daclatasvir. Huh7.5.1 cells infected with PR63cc or JFH1 at an MOI of 0.05 for 3 days were treated with either asunaprevir, daclatasvir or in combination for another 3 days. 40 nM asunaprevir and 0.05 nM daclatasvir, approximately the EC50 concentration of the each inhibitor for JFH1, were used. The antiviral efficiency of each compound was evaluated by quantifying the intracellular HCV RNA by RT-qPCR. Data were expressed as the percentage of mock treatment control. The error bars were calculated from two independent experiments. ns, P > 0.05. *, P < 0.05.

Data from [ , , Antiviral Res, 2017, 139:18-24 ]

Selleck's Daclatasvir (BMS-790052) Has Been Cited by 58 Publications

Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal imaging [ Structure, 2025, S0969-2126(25)00193-5] PubMed: 40553718
Hepatitis C virus-induced differential transcriptional traits in host cells after persistent infection elimination by direct-acting antivirals in cell culture [ J Med Virol, 2024, 96(7):e29787] PubMed: 38988177
Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa [ EMBO Mol Med, 2024, 16(4):870-884] PubMed: 38462666
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271
Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes [ J Virol, 2024, e0192123.] PubMed: 38319104
Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus [ Viruses, 2023, 15(4)981] PubMed: 37112961
Hepatitis C virus cell culture adaptive mutations enhance cell culture propagation by multiple mechanisms but boost antiviral responses in primary human hepatocytes [ bioRxiv, 2023, 2023.11.22.568224] PubMed: 38045248
Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture [ Commun Biol, 2022, 5(1):154] PubMed: 35194144
Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds [ Chemistry, 2022, e202202798.] PubMed: 36286339
Correlation of hepatitis C virus-mediated endoplasmic reticulum stress with autophagic flux impairment and hepatocarcinogenesis [ Med Mol Morphol, 2021, 10.1007/s00795-020-00271-5] PubMed: 33386512

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