High-power screening (HPS) empowered by DNA-encoded libraries

Trends Pharmacol Sci. 2022 Jan;43(1):4-15. doi: 10.1016/j.tips.2021.10.008. Epub 2021 Nov 12.

Abstract

The world is totally dependent on medications. As science progresses, new, better, and cheaper drugs are needed more than ever. The pharmaceutical industry has been predominantly dependent on high-throughput screening (HTS) for the past three decades. Considering that the discovery rate has been relatively constant, can one hope for a much-needed sudden trend uptick? DNA-encoded libraries (DELs) and similar technologies, that have several orders of magnitude more screening power than HTS, and that we propose to group together under the umbrella term of high-power screening (HPS), are very well positioned to do exactly that. HPS also offers novel screening options such as parallel screening, ex vivo and in vivo screening, as well as a new path to druggable alternatives such as proteolysis targeting chimeras (PROTACs). Altogether, HPS unlocks novel powerful drug discovery avenues.

Keywords: DNA-encoded library; drug discovery; high-power screening; high-throughput screening.

Publication types

  • Review

MeSH terms

  • DNA
  • Drug Discovery
  • Drug Industry
  • High-Throughput Screening Assays*
  • Humans
  • Small Molecule Libraries* / pharmacology

Substances

  • Small Molecule Libraries
  • DNA