Skip to Content
Merck
  • Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease.

Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease.

Antimicrobial agents and chemotherapy (2006-02-24)
Robert B Perni, Susan J Almquist, Randal A Byrn, Gurudatt Chandorkar, Pravin R Chaturvedi, Lawrence F Courtney, Caroline J Decker, Kirk Dinehart, Cynthia A Gates, Scott L Harbeson, Angela Heiser, Gururaj Kalkeri, Elaine Kolaczkowski, Kai Lin, Yu-Ping Luong, B Govinda Rao, William P Taylor, John A Thomson, Roger D Tung, Yunyi Wei, Ann D Kwong, Chao Lin
ABSTRACT

VX-950 is a potent, selective, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3-4A serine protease, and it demonstrated excellent antiviral activity both in genotype 1b HCV replicon cells (50% inhibitory concentration [IC50] = 354 nM) and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC50 = 280 nM). VX-950 forms a covalent but reversible complex with the genotype 1a HCV NS3-4A protease in a slow-on, slow-off process with a steady-state inhibition constant (K(i)*) of 7 nM. Dissociation of the covalent enzyme-inhibitor complex of VX-950 and genotype 1a HCV protease has a half-life of almost an hour. A >4-log10 reduction in the HCV RNA levels was observed after a 2-week incubation of replicon cells with VX-950, with no rebound of viral RNA observed after withdrawal of the inhibitor. In several animal species, VX-950 exhibits a favorable pharmacokinetic profile with high exposure in the liver. In a recently developed HCV protease mouse model, VX-950 showed excellent inhibition of HCV NS3-4A protease activity in the liver. Therefore, the overall preclinical profile of VX-950 supports its candidacy as a novel oral therapy against hepatitis C.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Telaprevir, ≥90% (HPLC)
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPrice
1 g
1 Estimated to ship on February 24, 2025
€243.00

To order products, please contact your local dealer.