VX-950 (Telaprevir) is an orally-available, highly-selective, reversible, peptidomimetic inhibitor of HCV NS3-4A protease with an IC50 of 0.35 uM and IC90 of 0.83 uM in an HCV replicon assay [1, 2] In human fetal hepatocytes with genotype 1a HCV-postive patient serum, VX-950 has an IC50 of 280 uM. [3] VX-950 reduces HCV RNA levels in a time- and dose-dependent manner with IC50s of 0.57, 0.49, 0.21, and 0.14 uM following a 24-, 48-, 72-, and 120-h incubation.

VX-950 forms a covalent, but reversible complex in a slow-on, slow-ff process with a steady-state inhibition constant (Ki) of 7 nM. [3] Excellent efficacy with high liver exposure in an HCV NS3-4A mouse model was observed with VX-950.