NMR in target driven drug discovery: why not?

J Biomol NMR. 2020 Nov;74(10-11):521-529. doi: 10.1007/s10858-020-00343-9. Epub 2020 Sep 8.

Abstract

No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.

Keywords: Biophysics; Fragment based drug discovery; Small molecule drug discovery; Structure based drug design.

MeSH terms

  • Crystallography / methods
  • Drug Discovery / methods*
  • High-Throughput Screening Assays
  • Ligands
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Proteins / chemistry*
  • Proteins / isolation & purification
  • Quantitative Structure-Activity Relationship
  • Small Molecule Libraries / chemistry
  • Solutions / chemistry

Substances

  • Ligands
  • Proteins
  • Small Molecule Libraries
  • Solutions