title: Lead Optimization in Discovery Drug Metabolism and Pharmacokinetics/Case study: The Hepatitis C Virus (HCV) Protease Inhibitor SCH 503034.
abstract: Lead optimization using drug metabolism and pharmacokinetics (DMPK) parameters has become one of the primary focuses of research organizations involved in drug discovery in the last decade. Using a combination of rapid in vivo and in vitro DMPK screening procedures on a large array of compounds during the lead optimization process has resulted in development of compounds that have acceptable DMPK properties. In this review, we present a general screening paradigm that is currently being used as part of drug discovery at Schering-Plough and we describe a case study using the Hepatitis C Virus (HCV) protease inhibitor program as an example. By using the DMPK optimization tools, a potent HCV protease inhibitor, SCH 503034, was selected for development as a candidate drug.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics.
authors.forename: K-C
authors.initials: KC
authors.lastname: Cheng
authors.forename: Walter A
authors.initials: WA
authors.lastname: Korfmacher
authors.forename: Ronald E
authors.initials: RE
authors.lastname: White
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge