Lead Optimization in Discovery Drug Metabolism and Pharmacokinetics/Case Study: The Hepatitis C Virus (HCV) Protease Inhibitor SCH 503034
Harold H. Trimm, William Hunter Jr. · Apple Academic Press eBooks · 2012
Introduction Lead optimization in a drug metabolism environment is a multifaceted operation. It typically involves the use of various in vitro and in vivo screens to assess the drug metabolism and pharmacokinetic (DMPK) properties of multiple compounds, as well as to provide an early check on the safety issues that can be assessed in a higher throughput manner [1-4]. is process involves interaction between DMPK scientists, biologists/pharmacologists and medicinal/physical chemists. e goal of the interaction is to nd a molecule that has the desired biological activity as well as DMPK properties and a safety prole appropriate for the targeted therapeutic indication. In this paper, we provide an overview of the DMPK lead optimization process that is used to support drug discovery projects at Schering-Plough. In addition, we will demonstrate how the process was used in a particular program (HCV protease inhibitor) as a case study.