BioCentury
ARTICLE | Distillery Therapeutics

Infectious disease

July 10, 2017 6:07 PM UTC

In vitro and cell culture studies identified analogs of the HCV NS3/4A protease complex inhibitor grazoprevir that could help treat drug-resistant HCV infections. Chemical synthesis and testing of grazoprevir analogs in vitro yielded five compounds that inhibited a drug-resistant variant of the protease complex with Ki values below 40 nM. In human cell-based replicon assays, four of the compounds inhibited replication of HCV strains engineered to express the variant and three additional drug-resistant variants of the protease complex with EC50 values below 4.5 nM. Next steps could include testing the compounds in animal model of HCV.

Merck & Co. Inc. has grazoprevir (MK-5172), an oral HCV NS3/4A protease inhibitor, in Phase III testing and markets Victrelis boceprevir, a small molecule HCV NS3/4A protease inhibitor, to treat HCV infection...