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Related Experiment Videos

Kinomics: characterizing the therapeutically validated kinase space.

Michal Vieth1, Jeffrey J Sutherland, Daniel H Robertson

  • 1Discovery Chemistry Research, Lilly Research Laboratories, Lilly Corporate Center, DC 1513, Indianapolis, IN 46285, USA. m.vieth@lilly.com

Drug Discovery Today
|June 23, 2005
PubMed
Summary
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Kinase inhibitors in clinical use are larger and more lipophilic than other drugs. Similar sequences in kinases suggest they can be targeted by the same drug classes, aiding drug discovery.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Structural Biology

Background:

  • Kinase inhibitors are crucial in targeted cancer therapy.
  • Understanding the chemical space of kinase inhibitors is vital for drug development.
  • Previous studies have explored kinase targets but lacked comprehensive analysis of their chemical properties and relationships.

Purpose of the Study:

  • To annotate and visualize the medicinally relevant kinase space.
  • To characterize the physicochemical properties of clinically used kinase inhibitors.
  • To identify relationships between kinase sequence similarity and drug targeting.

Main Methods:

  • Annotation and visualization of kinase data.
  • Comparative analysis of molecular weight and lipophilicity of kinase inhibitors versus other drugs.

Related Experiment Videos

  • Sequence, selectivity, and structural analysis of kinase targets.
  • Identification of sequence identity thresholds for shared drug targeting.

    • Main Results:

    • Clinically used kinase inhibitors exhibit higher average molecular weight and lipophilicity compared to other drugs.
    • Vascular endothelial growth factor and epidermal growth factor receptor tyrosine kinases are the most frequently targeted.
    • Oncological indications represent 75% of clinical interest in kinases.
    • Kinases with ≥60% sequence identity share similar ATP-binding sites and are targeted by similar compound classes.

    Conclusions:

    • The physicochemical properties of kinase inhibitors differ significantly from other drug classes.
    • Targeting specific kinase families, particularly in oncology, remains a primary focus.
    • A sequence identity threshold of 60% is identified as a predictor for shared drug targeting and similar ATP-binding sites.
    • This study enhances the understanding of the kinome's clinical and structural landscape, facilitating future drug discovery efforts.