title: Identification of small-molecule modulators of the circadian clock.
abstract: Chemical biology or chemical genetics has emerged as an interdisciplinary research area applying chemistry to understand biological systems. The development of combinatorial chemistry and high-throughput screening technologies has enabled large-scale investigation of the biological activities of diverse small molecules to discover useful chemical probes. This approach is applicable to the analysis of the circadian clock mechanisms through cell-based assays to monitor circadian rhythms using luciferase reporter genes. We and others have established cell-based high-throughput circadian assays and have identified a variety of novel small-molecule modulators of the circadian clock by phenotype-based screening of hundreds of thousands of compounds. The results demonstrated the effectiveness of chemical biology approaches in clock research field. This technique will become more and more common with propagation of high-throughput screening facilities. This chapter describes assay development, screening setups, and their optimization for successful screening campaigns.
authors: Molecular and Computational Biology Section, University of Southern California, Los Angeles, California, USA; Institute of Transformative Bio-Molecules, Nagoya University, Nagoya, Japan.
authors: Tsuyoshi
authors: T
authors: Hirota
authors: Molecular and Computational Biology Section, University of Southern California, Los Angeles, California, USA; Institute of Transformative Bio-Molecules, Nagoya University, Nagoya, Japan. Electronic address: alestell@usc.edu.
authors: Steve A
authors: SA
authors: Kay
mesh_terms: D000818:Animals; D002460:Cell Line; D057906:Circadian Clocks / Q000187:drug effects*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D054852:Small Molecule Libraries; D049409:Luciferases, Firefly
keywords: Chemical biology; Circadian period; Clock genes; High-throughput screening; Luciferase reporter; Robotics; Small-molecule compounds