Daclatasvir (BMS-790052)

製品コードS1482 バッチS148203

印刷

化学情報

Chemical Structure Synonyms EBP883 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C40H50N8O6
分子量 738.88 CAS No. 1009119-64-5
Solubility (25°C)* 体外 DMSO 148 mg/mL (200.3 mM)
Ethanol 148 mg/mL (200.3 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]
特徴 First-in-class, highly selective inhibitor of hepatitis C virus (HCV) NS5A with picomolar EC50 values.

プロトコル(参考用のみ)

キナーゼアッセイ 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。
細胞アッセイ 細胞株 HCV replicon cells (Huh7)
濃度 0.1 pM - 50 μM, dissolved in DMSO (the final concentration of DMSO is 0.5%)
反応時間 72 hours
実験の流れ 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.

参考

  • 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/

カスタマーフィードバック

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

, 2011, Dr. Anita Nag of Florida State University

, 2011, Dr. Anita Nag of Florida State University

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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