275 ADAM10, ADAM17 AND MMP2 ACTIVITIES IN HEPATIC STELLATE CELLS ARE INVOLVED IN CX3CL1 PROCESSING AND CONTRIBUTE TO CHRONIC LIVER INJURY
323 PRECLINICAL PHARMACOKINETIC AND SAFETY PROFILE OF IDX375, A NOVEL AND POTENT NON-NUCLEOSIDE HCV POLYMERASE INHIBITOR
Hepatitis C virus (HCV) is a common blood-borne pathogen annually • infecting three to four million people worldwide. Currently, an estimated 170 million people are infected globally.1 The current standard-of-care therapy, a combination of pegylated • interferon and ribavirin, is effective in only 50% of patients infected with genotype 1 HCV and is associated with significant side effects. Thus, there remains a need for new, more effective and better tolerated HCV treatment options.2,3 The HCV polymerase is an attractive antiviral target. Nucleoside analogs • or, more recently, pro-nucleotides such as IDX184, which target the active site of the enzyme, are currently in clinical trials. In another approach, multiple classes of non-nucleoside polymerase inhibitors (NNI), which target different allosteric sites of the enzyme, are under investigation. IDX375 is a novel NNI clinical candidate that targets the palm pocket of the • NS5B polymerase. This study evaluated the preclinical pharmacokinetics, in vitro metabolism and preliminary toxicology profiles of IDX375.