product name Daclatasvir (BMS-790052)
Description: Daclatasvir (also known as BMS-790052 and EBP-883 ) is a highly potent and 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. Daclatasvir is used for the treatment of hepatitis C (HCV). It is was developed by Bristol-Myers Squibb and was approved in EU in 2014. Daclatasvir inhibits the HCV nonstructural protein NS5A. Recent research 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.
738.88
Formula
C40H50N8O6
CAS No.
1009119-64-5
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)
Solubility (In vivo)
Synonyms
BMS-790052 and EBP-883
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19424092
| 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-790052s 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: 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 Vivo | A phase I clinical study showed Daclatasvir’s inhibition for HCV viruses. A 1 mg dose of daclatasvir produced a mean 1.8 log10 reduction in serum HCV RNA 24 h after administration. The 10 and 100 mg doses produced 3.2 log10 and 3.3 log10 reductions, respectively. Data collected from clinical trials on daclatasvir illustrated an initial, rapid viral decline followed by a slower fall in HCV RNA, which indicated that by inhibiting NS5A, daclatasvir blocks intracellular HCV RNA synthesis and virion assembly and secretion. |
| Animal model | |
| Formulation & Dosage | |
| 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. |
