BMS-790052 is a first-in-class, nonstructural protein 5A (NS5A) replication complex inhibitor with an EC50 of 9-50 pM. It is one of the most potent inhibitors of HCV replication reported so far. 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. BMS-790052 was well tolerated in all dose groups, with adverse events occurring with a similar frequency in BMS-790052- and placebo-treated groups. BMS-7590052 is the first NS5A replication complex inhibitor with multiple dose proof-of-concept in clinic. At doses of 1-100 mg daily, BMS-790052 was well tolerated, had a PK profile supportive of once-daily dosing, and produced a rapid and substantial decrease in HCV-RNA levels in patients chronically infected with HCV genotype 1.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO ≥100 mg/mL
Ethanol ≥100 mg/mL
Effect on HCV Replication by Combinations of Direct Acting Antivirals Including NS5A Inhibitor Daclatasvir.
Pelosi et al. Antimicrob Agents Chemother. 2012 Jul 30. PMID: 22850513.
Correlation between NS5A Dimerization and Hepatitis C Virus Replication.
Lim et al. J Biol Chem. 2012 Aug 31;287(36):30861-73. PMID: 22801423.
Hepatitis C Virus NS5A Disrupts STAT1 Phosphorylation and Suppresses Type I Interferon Signaling.
Kumthip et al. J Virol. 2012 Aug;86(16):8581-91. PMID: 22674974.
Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b.
Suzuki et al. J Clin Virol. 2012 Aug;54(4):352-4. PMID: 22658798.
A sensitive and accurate liquid chromatography-tandem mass spectrometry method for quantitative determination of the novel hepatitis C NS5A inhibitor BMS-790052 (daclastasvir) in human plasma and urine.
Jiang et al. J Chromatogr A. 2012 Jul 6;1245:117-21. PMID: 22640838.
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