Amphihevir is a potent, selective HCV NS4B inhibitor with EC50 of 0.34 and 1.97 nM against the GT1a (H77) and GT1b replicon in luciferase assays.
Amphihevir shows weaker acitivity against GT2a (JFH-1) (EC50=186 nM).
Amphihevir shows EC50 3.13 nM and 18.16 nM with 100% human serum against GT1a and GT1b replicons using HCV-1b replicon cells test.
Amphihevir reduced replicon RNA by nearly 6,300-fold (3.8 log10) at a concentration 25-fold greater than the EC90 (300 nM).
Amphihevir was found to be inactive against other viruses, human kinases, and GPCRs, which implies its good selectivity.
Amphihevir has good oral bioavailability and appropriate T1/2 in rats and dogs, showed good safety profiles in rats and dogs.
Amphihevir is the first reported NS4B inhibitor that has advanced to clinical trials.
