Description
HBV-IN-4, a phthalazinone derivative, is a potent and orally active HBV DNA replication inhibitor with an IC 50 of 14 nM. HBV-IN-4 induces the formation of genome-free capsids and has potent anti- HBV potenciesIn VitroHBV-IN-4 (compound 19f; 0-1 µM; 8 days) treatment inhibits the various forms (relaxed circular [rc] and single-stranded [ss] HBV DNA) in a dose-dependent manner in HepG2.2.15 cells. HBV-IN-4 treatment could also reduce capsidassociated DNAs dose-dependently. HBV-IN-4 could induce the formation of genome-free capsids, including a phenotype of faster-migrating ones. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoHBV-IN-4 (Compound 19f; 50-150 mg/kg; oral administration; twice a day; for 4 weeks; Balb/c male mice) treatment achieves 2.67 log viral load reduction in AAV-HBV/mouse model. HBV-IN-4 (compound 19f) exhibits favorable drug characteristics with low plasma clearance (CL=4.1 mL/min/kg), excellent drug exposure (AUC 0-t =49 744 h•ng/L), T 1/2 (2.15 hours) and oral bioavailability (F=60.4%) using 20 mg/kg oral administration in mice. HBV-IN-4 also shows good distribution in liver exposure. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Balb/c male mice (8-week-old) injected with a recombinant adenoassociated virus (AAV Dosage: 50 mg/kg, 150 mg/kg Administration: Oral administration; twice a day; for 4 weeks Result: Resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment.IC50& Target:IC50: 14 nM (HBV DNA replication)