High-Throughput Cell Toxicity Assays.
Understanding compound-driven cell toxicity is vitally important for all drug discovery approaches. With high-throughput screening (HTS) being the key strategy to find hit and lead compounds for drug discovery projects in the pharmaceutical industry [1], an understanding of the cell toxicity profile of hit molecules from HTS activities is fundamentally important. Recently, there has been a resurgence of interest in phenotypic drug discovery and these cell-based assays are now being run in HTS labs on ever increasing numbers of compounds. As the use of cell assays increases the ability to measure toxicity of compounds on a large scale becomes increasingly important to ensure that false hits are not progressed and that compounds do not carry forward a toxic liability that may cause them to fail at later stages of a project. Here we describe methods employed in the AstraZeneca HTS laboratory to carry out very large scale cell toxicity screening.
Discovery Sciences, Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, SK10 4TG, UK. david.murray@astrazeneca.com.
David
D
Murray
Discovery Sciences, Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, SK10 4TG, UK.
Lisa
L
McWilliams
Discovery Sciences, Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, SK10 4TG, UK.
Mark
M
Wigglesworth
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005453:Fluorescence; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D018675:Toxicity Tests / Q000379:methods*
Apoptosis; Cell-based assays; HTS; High-throughput screening; Phenotypic; Resazurin; Toxicity