PHX1766

PHX1766 is an orally bioavailable small molecule inhibitor of the Hepatitis C Virus (HCV) NS3/4A serine protease, developed by Phenomix Corporation for the treatment of chronic HCV infection. As a boronic acid derivative, PHX1766 targets the active site of the NS3/4A protease, an enzyme essential for the proteolytic cleavage of the viral polyprotein into mature non-structural proteins required for viral replication. In preclinical studies, the compound demonstrated high potency against HCV replicons with a 50% maximal effective concentration (EC50) of 8 nM. Although Phase I clinical trials in healthy volunteers and patients with HCV genotype 1 established that the drug was safe and well-tolerated with a favorable pharmacokinetic profile, it achieved only a modest mean maximal HCV RNA reduction of 1.5 log10 IU/ml after six days of monotherapy. Due to this limited clinical efficacy relative to other protease inhibitors in development at the time, further development of PHX1766 was discontinued.