tcsc0338 Simeprevir

Simeprevir is a potent HCV NS3/4A protease inhibitor, and inhibits HCV replication with EC₅₀ of 8 nM.

IC50 & Target: EC50: 8 nM

In Vitro: In Huh7-Luc cells, antiviral activity of simeprevir (TMC435350) is dose dependent, and the EC₅₀ and EC₉₀ values determined for TMC435350 are 8 nM and 24 nM, respectively. Inhibition of TMC435350 on NS3/4A protease is time dependent, and the overall K_is are estimated to be 0.5 nM for genotype 1a and 0.4 nM for genotype 1b, respectively^[1]. TMC435350 is a potent inhibitor of HCV NS3/4A protease (K_i=0.36 nM) and viral replication (replicon EC₅₀=7.8 nM)^[2].

In Vivo: In rats, TMC435350 (40 mg/kg, p.o.) is extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability is 44%^[1].