ABSTRACT
INTRODUCTION This chapter reviews advantages and shortcomings of cell-based assays for highthroughput screening (HTS) and identifies emerging trends in information-rich cell-based formats with throughput comparable to traditional cell-free biochemical screens. During the last decade, HTS has become an integrated part of the drug discovery engine for lead identification. Technological advances in assay miniaturization now enable screens in excess of one million member compound libraries in a short period of time, thus producing multiple starting points for medicinal chemistry (1,2). Because many active molecules can be identified quickly during primary HTS campaigns, hit assessment and prioritization of the target-specific chemical entities becomes a next critical step. The major challenge during lead optimization is to generate quantitative and predictive results to yield high-quality leads. The increasing sophistication of compound testing in biologically relevant cell-based assays encompassing complex functional systems enhances the probability of success by aligning in vitro and in vivo assessment of compound activity. A recent survey of 58 HTS laboratories and 34 suppliers reported that cell-based screens comprise on average 50% of all the assays currently utilized in support of drug discovery (3).
