ABSTRACT
INTRODUCTION High-throughput screening (HTS) is a key process in modern drug discovery, as it serves to reveal novel chemical leads from large compound libraries. Efficient and rapid translation of HTS efforts in to lead optimization, and subsequently, clinical candidates, requires that HTS campaigns yield near drug-like hits with substantial structure-activity relationship (SAR) information upfront to get a head start. A recent analysis of HTS practices in the industry revealed that on an average about 50% of the targets screened in HTS resulted in leads (1). Of the leads, 104 drug candidates made it into human testing and clinical trials. This number is trending upwards, due in part to the increasing number of laboratories that undertake HTS campaigns, which further underscores the importance of HTS in drug discovery. Thus, HTS necessitates the screening of increasingly large compound libraries in a highly industrialized and automated setting. Although the chemical composition of the library is unarguably a critical component of this process, the other equally important step is the design of sensitive and reliable assays that will serve as markers of compound activity. This chapter focuses on the use of cell-based assays as primary highthroughput screens, and more specifically, the recent advances in availability of cells for large-scale screens that are resulting in noteworthy trends in HTS practices.
