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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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High-throughput kinetics in drug discovery.

Maria Filipa Pinto1, Julija Sirina2, Nicholas D Holliday3

  • 1Artios Pharma Ltd, B940, Babraham Research Campus, Cambridge CB22 3FH, United Kingdom.

SLAS Discovery : Advancing Life Sciences R & D
|July 4, 2024
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Summary

Advances in drug discovery now allow for early kinetic characterization. Improved techniques and data analysis enable faster understanding of structure-kinetic relationships and their impact on pharmacokinetics/pharmacodynamics (PK/PD).

Keywords:
Enzyme kineticsHigh-throughputMechanism of inhibition (MoI)

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Area of Science:

  • Pharmacology
  • Drug Discovery
  • Biochemistry

Background:

  • The significance of drug kinetic profiles and structure-kinetic activity relationships in drug discovery is well-established.
  • Historically, technical hurdles have restricted detailed kinetic characterization to later stages of drug development projects.

Purpose of the Study:

  • To review recent advancements in techniques, instrumentation, and data analysis for kinetic characterization.
  • To highlight how these improvements facilitate earlier application of kinetic studies in drug discovery.

Main Methods:

  • Review of recent literature on high-throughput kinetic assays.
  • Analysis of innovations in analytical instrumentation for kinetic measurements.
  • Examination of novel data analysis methodologies for kinetic data.

Main Results:

  • Significant progress has been made in increasing the throughput of detailed kinetic and mechanistic characterization.
  • New technologies allow for more comprehensive kinetic profiling earlier in the drug discovery pipeline.
  • Enhanced data analysis tools improve the interpretation of complex kinetic data.

Conclusions:

  • Recent technological and analytical advances enable earlier and more efficient kinetic characterization of drug candidates.
  • This facilitates a better understanding of pharmacokinetics/pharmacodynamics (PK/PD) relationships early in the discovery process.
  • Accelerated kinetic assessment can significantly streamline drug discovery and development timelines.