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Updated: Jun 6, 2026
13:22
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Trends in kinase selectivity: insights for target class-focused library screening
Shana L Posy1, Mark A Hermsmeier, Wayne Vaccaro
1Computer-Assisted Drug Design, Applied Biotechnology, Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, United States.
Journal of Medicinal Chemistry
|December 7, 2010
Summary
Researchers screened over 20,000 compounds against kinases, finding diverse scaffolds achieve specificity. Kinase selectivity and potency are inversely correlated, guiding future drug discovery efforts.
Area of Science:
- Medicinal Chemistry
- Biochemistry
- Pharmacology
Background:
- Kinase inhibitors are crucial therapeutics, but achieving selectivity remains a challenge.
- Understanding structure-activity relationships is key for developing targeted therapies.
Purpose of the Study:
- To conduct a comprehensive kinome-wide selectivity screen of over 20,000 compounds.
- To analyze selectivity patterns across diverse structural scaffolds and kinase families.
- To identify physicochemical features associated with kinase binding promiscuity.
Main Methods:
- Performed a kinome-wide screening assay using a diverse chemical library (>20,000 compounds).
- Analyzed selectivity profiles for different compound structural classes.
- Correlated kinase selectivity and potency with physicochemical properties.
Main Results:
- Identified broad structural scaffolds capable of achieving specificity across multiple kinase families.
- Confirmed an inverse correlation between kinase selectivity and compound potency.
- Discovered specific physicochemical features enriched in multi-kinase binders.
Conclusions:
- A scaffold-oriented approach is effective for designing compound libraries for kinase screening.
- Understanding selectivity patterns aids in the rational design of more specific kinase inhibitors.
- Physicochemical profiling can help predict compound polypharmacology.
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