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Updated: Mar 28, 2026
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Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
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On-rate based optimization of structure-kinetic relationship--surfing the kinetic map
1Proteros biostructures GmbH, Bunsenstrasse 7a, 82152 Martinsried, Germany.
Drug Discovery Today. Technologies
|January 3, 2016
Summary
Understanding structure-kinetic relationships (SKR) is crucial for optimizing drug compounds. This review highlights the on-rate as a key parameter for monitoring SKR, aiding in the development of efficacious compounds.
Area of Science:
- Drug discovery and medicinal chemistry
- Pharmacokinetics and pharmacodynamics
- Chemical biology
Background:
- Residence time is a critical parameter in lead discovery for identifying efficacious compounds in vivo.
- Understanding structure-kinetic relationships (SKR) is essential for successful compound optimization toward desired residence times.
Purpose of the Study:
- To review various approaches for monitoring SKR.
- To propose the on-rate as the key parameter for monitoring SKR.
- To discuss findings and rationales for kinetic on-rate changes.
Main Methods:
- Literature review of SKR monitoring approaches.
- Analysis of compound series with varying on-rates.
- Discussion of underlying rationales for observed kinetic changes.
Main Results:
- The on-rate is identified as a pivotal parameter for monitoring SKR.
- Examples of compound series with both low variability and significant on-rate changes are presented.
- Findings on kinetic on-rate changes and their potential rationales are discussed.
Conclusions:
- Monitoring the on-rate is essential for medicinal chemists to optimize compounds for desired residence times.
- A deeper understanding of SKR, particularly on-rate kinetics, can significantly improve the lead discovery process.
- Further investigation into the rationales behind kinetic on-rate changes is warranted.
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