Steady-state was achieved within 5 days of MK-87425-100 mg QD administration. KPT-330 manufacturer The range of accumulation ratios (day 5/1) for AUC0-24hr was 1.2-3.0. MK-8742 was generally well-tolerated, with all AEs transient and mild in intensity. The most common AE was headache. There were no clinically significant laboratory abnormalities, changes in vital signs or ECG readings. Conclusions: MK-8742 exhibits potent antiviral activity during 5 days of monotherapy in patients with GT-1 and GT-3 chronic HCV infection. The

safety, pharmacokinetics, and antiviral data support the continued clinical investigation of MK-8742 as a once-daily component of an all-oral, interferon-free regimen for the treatment of chronic HCV-infection. Disclosures: Wendy W. Yeh – Employment: Ipilimumab research buy Merck & Co. Patricia Jumes – Employment: Merck; Stock Shareholder: Merck Inge M. De Lepeleire – Management Position: MSD (Europe) Inc. ; Stock Shareholder: Merck & co., Inc. Luzelena Caro – Employment: Merck & Co., Inc. Eric Mangin – Employment: Merck & Co., Inc. Robert B. Nachbar – Employment: Merck Sharp & Dohme Corp.; Stock Shareholder: Merck Sharp &

Dohme Corp. Edward J. Gane-Advisory Committees or Review Panels: Roche, AbbVie, Novartis, Tibotec, Gilead Sciences, Janssen Cilag, Vertex, Achillion; Speaking and Teaching: Novartis, Gilead Sciences, Roche Joan R. Butterton – Employment: Merck Sharp & Dohme Corp.; Stock Shareholder: Merck Sharp & Dohme Corp. The following people have nothing to disclose: Concetta Lipardi, Nick Van Den Bulk, Xiaobi Huang, Serghei Popa, Nelea Ghicavii, Frank D. Wagner About 3 % of world population is persistently infected with hepatitis C virus (HCV) and at increased risk of fatal chronic liver diseases such as cirrohsis and hepatocellular carcinoma. Because the efficacy of current therapy with pegylated IFN and ribavirin is insufficient and depends medchemexpress in part on viral genotypes, there is great interest in development

of novel HCV-specific inhibitors. The development of new molecule that targets HCV protein called direct-acting antivirals is ongoing. Nonstructural protein 5A (NS5A) of HCV plays multiple and diverse roles in the viral lifecycle, and is currently recognized as a novel target for anti-viral therapy. In 2010, the first-generation NS5A inhibitor has been reported as to reduce the viral titer significantly after oral administration. However, it shows limited effects on genotype 2 HCV strains other than JFH-1 strain in cell culture system. Recently, to overcome this disadvantage, the second-generation NS5A inhibitors have been developed. The aim of this study was to evaluate the genotype-specific antiviral effects of these novel NS5A inhibitors. To assess the genotype-specificity of NS5A inhibitors, recombinant JFH-1 viruses replaced with NS5A of genotypes 1 (H77; 1a and Con1; 1b) and 2 (J6CF; 2a, MA; 2b and J8; 2b) were used.