Simeprevir

A potent, orally available inhibitor of HCV NS3/4A protease with Ki of 0.36 nM, replicon EC50 of 7.8 nM; inhibits NS3/4A proteases of genotypes 1a and 1b with Ki of 0.5 and 0.4 nM, shows synergistic effect with α-Interferon and an NS5B inhibitor in the replicon model and additive with ribavirin; exerts favorable pharmacokinetic profile and antiviral activity in vivo.HCV Infection Approved (In Vitro) :Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50 and EC90 values of 8 nM and 24 nM, respectively.Simeprevir (TMC435) inhibits NS3/4A proteases from HCV genotypes 1 to 6 with IC50s of 1/0.9/7/30/1.5/2.2/1.6 nM for 1a/1b/2b/3a/4/5/6, respectively.Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with IC50s of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively. (In Vivo) :Simeprevir (TMC435) has moderate terminal elimination half-life (t1/2=1.5 h and 4.1 h for rat (3 mg/kg, p.o.), monkey (3 mg/kg, p.o.) ) .Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance.