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Updated: Oct 13, 2025

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

Yashoda Krishna Sunkari1, Vijay Kumar Siripuram1, Thu-Lan Nguyen1

  • 1Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.

Trends in Pharmacological Sciences
|November 16, 2021
PubMed
Summary

High-power screening (HPS), including DNA-encoded libraries (DELs), offers significantly greater screening power than traditional methods. This advancement promises to accelerate drug discovery and enable new therapeutic modalities like PROTACs.

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Area of Science:

  • Drug Discovery and Development
  • Medicinal Chemistry
  • Biotechnology

Background:

  • Global reliance on pharmaceuticals necessitates continuous innovation in drug development.
  • The pharmaceutical industry has relied on high-throughput screening (HTS) for over 30 years.
  • Current drug discovery rates remain stagnant despite technological advancements.

Purpose of the Study:

  • To introduce and define High-Power Screening (HPS) as a transformative approach in drug discovery.
  • To highlight the potential of HPS technologies, such as DNA-encoded libraries (DELs), to overcome limitations of traditional HTS.
  • To explore novel screening capabilities and therapeutic modalities enabled by HPS.

Main Methods:

  • Grouped advanced screening technologies, including DNA-encoded libraries (DELs), under the umbrella term High-Power Screening (HPS).
Keywords:
DNA-encoded librarydrug discoveryhigh-power screeninghigh-throughput screening

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  • Compared the screening capacity of HPS with conventional high-throughput screening (HTS).
  • Identified novel applications of HPS, including parallel, ex vivo, and in vivo screening.

    • Main Results:

    • HPS technologies offer several orders of magnitude greater screening power compared to HTS.
    • HPS enables innovative screening strategies beyond traditional HTS capabilities.
    • HPS provides a pathway for developing novel druggable alternatives, such as proteolysis targeting chimeras (PROTACs).

    Conclusions:

    • High-Power Screening (HPS) is poised to significantly increase the rate of drug discovery.
    • HPS unlocks powerful new avenues for identifying and developing next-generation therapeutics.
    • The adoption of HPS technologies is crucial for meeting the growing global demand for effective medications.