High-throughput screening: today's biochemical and cell-based approaches

V Blay, B Tolani, SP Ho, MR Arkin - Drug Discovery Today, 2020 - Elsevier
Drug Discovery Today, 2020Elsevier
Highlights•Self-contained overview of current high-throughput screening technologies.•
Expands on the current use of most recent tools, like high-throughput microscopy.•Learn
about recent developments in target identification, including CRISPR screens.•Provides
suggestions for screening decisions and directions for future research.High-throughput
screening (HTS) provides starting chemical matter in the adventure of developing a new
drug. In this review, we survey several HTS methods used today for hit identification …
Highlights
  • Self-contained overview of current high-throughput screening technologies.
  • Expands on the current use of most recent tools, like high-throughput microscopy.
  • Learn about recent developments in target identification, including CRISPR screens.
  • Provides suggestions for screening decisions and directions for future research.
High-throughput screening (HTS) provides starting chemical matter in the adventure of developing a new drug. In this review, we survey several HTS methods used today for hit identification, organized in two main flavors: biochemical and cell-based assays. Biochemical assays discussed include fluorescence polarization and anisotropy, FRET, TR-FRET, and fluorescence lifetime analysis. Binding-based methods are also surveyed, including NMR, SPR, mass spectrometry, and DSF. On the other hand, cell-based assays discussed include viability, reporter gene, second messenger, and high-throughput microscopy assays. We devote some emphasis to high-content screening, which is becoming very popular. An advisable stage after hit discovery using phenotypic screens is target deconvolution, and we provide an overview of current chemical proteomics, in silico, and chemical genetics tools. Emphasis is made on recent CRISPR/dCas-based screens. Lastly, we illustrate some of the considerations that inform the choice of HTS methods and point to some areas with potential interest for future research.
Elsevier