title: Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection.
abstract: Boceprevir is an HCV NS3 (non-structural protein 3) serine protease inhibitor being developed by Schering-Plough Corp as a capsule formulation. In pharmacokinetic studies, boceprevir was adequately absorbed, with the most effective mode of administration appearing to be a three-times-daily regimen. In phase I clinical trials, monotherapy with boceprevir led to a distinct viral load reduction. In phase Ib combination trials of boceprevir with PEGylated IFNalpha2b and ribavirin, the reduction in viral replication was further increased. Early data reported from phase II clinical trials have been promising, suggesting a rapid early HCV-RNA reduction. Phase III trials for the drug began in 2008. Results available to date have demonstrated the compound to be well tolerated, with adverse events that were within the range of current standard-of-care therapy. Thus, boceprevir may have the potential to increase sustained virological response rates and possibly also to shorten duration of therapy; data from ongoing clinical trials are awaited.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Mederacke
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
mesh_terms: D000818:Animals; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D015394:Molecular Structure; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002214:Capsules; D004338:Drug Combinations; D011392:Proline; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide