Binding kinetics and mechanism of action: toward the discovery and development of better and best in class drugs

doi:10.1517/17460441.2010.520700

Paper

Binding kinetics and mechanism of action: toward the discovery and development of better and best in class drugs

Published Oct 22, 2010 · Rumin Zhang, F. Monsma

Expert Opinion on Drug Discovery

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83

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1

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Abstract

Binding kinetics (BK), an often overlooked key aspect of the broader concept of drug mechanism of action (MOA), is increasingly recognized as a springboard from pharmacokinetics (PK) to pharmacodynamics, and as a critical differentiator and predictor for drug efficacy and safety. Just as greater attention to PK issues has helped reduce the attrition of drugs tested in clinical trials, the emerging paradigm shift from primarily affinity/potency-emphasized to a more holistic BK-perceptive and MOA-informed approach is expected to further enhance the success of drug discovery and development. This perspective attempts to envision what this new approach looks like when proper emphasis is placed on BK and MOA in designing better and best in class drugs.

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Study Snapshot

Proper emphasis on binding kinetics and mechanism of action can enhance the success of drug discovery and development, leading to better and best-in-class drugs.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Binding kinetics and mechanism of action: toward the discovery and development of better and best in class drugs

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References

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Optimizing high-throughput screens for allosteric ligands can enhance the detection of potential therapeutic drugs and improve therapeutic targeting.

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Systems pharmacology, which utilizes network analysis of drug action, can lead to new therapeutic options and improved safety and efficacy of existing medications by considering drug actions in the context of the whole genome.

Citations

Decoding Inhibitor Egression from Wild-Type and G2019S Mutant LRRK2 Kinase: Insights into Unbinding Mechanisms for Precision Drug Design in Parkinson's Disease.

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Accurate Characterization of Binding Kinetics and Allosteric Mechanisms for the HSP90 Chaperone Inhibitors Using AI-Augmented Integrative Biophysical Studies

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Novel 6-alkyl-bridged 4-arylalkylpiperazin-1-yl derivatives of azepino[4,3-b]indol-1(2H)-one as potent BChE-selective inhibitors showing protective effects against neurodegenerative insults.

Two novel compounds, 14c and 14d, show potential as BChE-selective inhibitors with more than two order magnitude of selectivity over AChE, potentially offering a new treatment for Alzheimer's disease and other CNS disorders.

Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action

Zelavespib extends on-target residence time in cancer and neurodegenerative diseases by trapping epichaperomes, leading to disassembly and a slower off-rate than expected from tumor pharmacokinetic profiles.

Nutraceuticals and Their Contribution to Preventing Noncommunicable Diseases

Nutraceuticals, found in functional foods, can help prevent and treat noncommunicable diseases by promoting early dietary intake.