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Area of Science:

  • Biophysics
  • Drug Discovery
  • High-Throughput Screening (HTS)

Background:

  • Biophysics has emerged as a key discipline in HTS hit triaging over the last decade.
  • Its high fidelity in detecting protein-ligand interactions makes it valuable for filtering HTS output.
  • Many pharmaceutical companies currently employ biophysical techniques for this purpose.

Purpose of the Study:

  • To review the established role of biophysics in HTS hit triaging.
  • To demonstrate the greater impact of applying biophysics earlier in the HTS assay development stage.
  • To highlight the importance of early mode-of-action studies and ensuring assay fitness-for-purpose.

Main Methods:

  • Review of biophysical techniques used in HTS hit triaging.
  • Analysis of 20 in-house projects to demonstrate the impact of early biophysical application.
  • Discussion of mode-of-action studies and assay validation strategies.

Main Results:

  • Biophysical methods are widely used to filter HTS output, reducing false positives.
  • Early integration of biophysics in assay development leads to more impactful outcomes.
  • Case studies from 20 projects illustrate the benefits of these approaches.

Conclusions:

  • Biophysics is essential for accurate HTS hit triaging and validation.
  • Proactive application of biophysics during assay development optimizes the drug discovery pipeline.
  • Ensuring assay fit-for-purpose through biophysical studies is critical for success.