HBV-IN-4, a derivative of phthalazinone, functions as a potent, orally active inhibitor of HBV DNA replication, exhibiting an IC50 value of 14 nM. It effectively induces the formation of genome-free capsids, demonstrating significant anti-HBV potency[1].

HBV DNA replication:14 nM (IC50)

HBV-IN-4 (compound 19f; 0-1 μM; 8 days) effectively inhibits relaxed circular [rc] and single-stranded [ss] HBV DNA in a dose-dependent manner in HepG2.2.15 cells. It also decreases capsid-associated DNAs and promotes genome-free capsids, particularly those with accelerated migration phenotype[1].

HBV-IN-4 (Compound 19f; 50-150 mg/kg; oral administration; twice a day; for 4 weeks; Balb/c male mice) achieves a 2.67 log viral load reduction in the AAV-HBV/mouse model[1]. It exhibits favorable drug characteristics, including low plasma clearance (CL=4.1 mL/min/kg), excellent drug exposure (AUC0-t=49,744 h·ng/L), T1/2 (2.15 hours), and oral bioavailability (F=60.4%) with 20 mg/kg oral administration in mice. HBV-IN-4 also shows good liver exposure distribution[1].