High-throughput screening assays for the identification of chemical probes.
High-throughput screening (HTS) assays enable the testing of large numbers of chemical substances for activity in diverse areas of biology. The biological responses measured in HTS assays span isolated biochemical systems containing purified receptors or enzymes to signal transduction pathways and complex networks functioning in cellular environments. This Review addresses factors that need to be considered when implementing assays for HTS and is aimed particularly at investigators new to this field. We discuss assay design strategies, the major detection technologies and examples of HTS assays for common target classes, cellular pathways and simple cellular phenotypes. We conclude with special considerations for configuring sensitive, robust, informative and economically feasible HTS assays.
Inglese
James
J
US National Institutes of Health Chemical Genomics Center, National Institutes of Health, 9800 Medical Center Drive, Bethesda, Maryland 20892-3370, USA. jinglese@mail.nih.gov
Johnson
Ronald L
RL
Simeonov
Anton
A
Xia
Menghang
M
Zheng
Wei
W
Austin
Christopher P
CP
Auld
Douglas S
DS
D000818:Animals; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D004798:Enzymes / Q000737:chemistry; D006801:Humans; D007477:Ions; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014158:Transcription, Genetic
D004798:Enzymes; D007477:Ions; D043562:Receptors, G-Protein-Coupled