The Problems of Applying Classical Pharmacology to Modern Drug Discovery

Pharmacology data analysis was developed a century ago and is used by default in modern drug discovery to quantify ligand potency for drug targets. This video describes the problems that can result when largely forgotten assumptions of classical pharmacology are infringed, by modern assay technology and very high affinity drugs and drug candidates. These assumptions are:
1) The target concentration is much less than the ligand concentration.
2) The target ligand interaction has reached equilibrium.
When these assumptions are broken, incorrect measurements of ligand potency can result, which distorts SAR in medicinal chemistry, hampers the selection of candidate drug molecules, and potentially interferes with human dosing prediction.
With real-world examples, the problems we encounter when these assumptions are broken are described, together with simple practical solutions that can ensure robust measurements of ligand potency.
The slides are available at this link, from which you can access the links to the cited papers and videos:
drive.google.c...
An associated video on binding kinetics is available on RUclips:
• Kinetics of Drug-Targe...
Simulators for investigating target concentration and equilibration issues are available for free at this link:
drive.google.c...
Thanks to Sarine Markossian, Jayme Dahlin and Marc Navre for support and encouragement in the development of this presentation.