Bay 41-4109 (less active enantiomer)

Bay 41-4109 less active enantiomer shows less activity than Bay 41-4109. BAY 41-4109 is a potent inhibitor of human hepatitis B virus (HBV) with an IC₅₀ of 53 nM. IC50 & Target: IC50: 53 nM (HBV, Bay 41-4109)^[1] In Vitro: BAY 41-4109 is able to both accelerate and misdirect capsid assembly in vitro. Preformed capsids are stabilized by BAY 41-4109, up to a ratio of one inhibitor molecule per two dimers^[2]. BAY 41-4109 is equally effective at inhibiting HBV DNA release and the cytoplasmic HBcAg level, with IC₅₀s of 32.6 and 132 nM in HepG2.2.15 cells, respectively. HBV DNA and HBcAg are inhibited in a dose-dependent manner, indicating that the anti-HBV mechanisms are associated with and dependent on the rate of HBcAg inhibition^[3]. In Vivo: BAY 41-4109 reduces viral DNA in the liver and in the plasma dose-dependently with efficacy comparable to 3TC. BAY 41 -4109 reduces hepatitis B virus core antigen (HBcAg) in livers of HBV-transgenic mice. Pharmacokinetic studies in mice have shown rapid absorption, a bioavailability of 30% and dose-proportional plasma concentrations, about 60% in rats and dogs^[1]. BAY41-4109 inhibits virus production in vivo by a mechanism that targets the viral capsid^[2].