Quality control of cell-based high-throughput drug screening

Abstract

The pharmaceutical industry is presently suffering difficult times due to low productivity of new molecular entities. As a major source of drug leads, high-throughput screening (HTS) has been often criticized for its ‘dead end’ lead compounds. However, the fruitful achievements resulting from HTS technology indicate that it remains a feasible way for drug innovation. Because of increasing considerations of earlier stage ADMET (absorption, distribution, metabolism, excretion and toxicity) in drug development, cell-based HTS is highly recommended in modern drug discovery for its ability to detect more biologically relevant characteristics of compounds in living systems. This review provides a systematic and practical description of vital points for conducting high quality cell-based HTS, from assay development to optimization, compound management, data analyses, hit validation as well as lead identification. Potential problems and solutions are also covered.