Biochem/physiol Actions
Orally active, non-cytotoxic, potent and genotype 1 replicons-selective non-nucleoside inhibitor (NNI) against hepatitis C virus (HCV).
Tegobuvir (GS-9190; TGV) is an orally active, non-cytotoxic imidazopyridine that, upon CYP-mediated intracellular activation, forms a glutathione conjugate that acts as a covalent, potent and genotype 1 replicons-selective non-nucleoside inhibitor (NNI) against hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (IC50 = 0.8 nM/1b, 13.8 nM/1a, 21.9 μM/2a, >50 μM/1a; IC50 >100 nM against 2b, 3a, 4a, 5a, and 6a). When combined with suboptimal concentrations of other direct acting antivirals (DAAs) in cultures, tegobuvir (6-30 nM) is highly effective in curing cells from HCV replicon and in delaying or preventing the development of resistance against other DAAs.