The Human Kinome and Kinase Inhibition

Krisna C. Duong‐Ly1, Jeffrey R. Peterson1

1 Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 2.9
DOI:  10.1002/0471141755.ph0209s60
Online Posting Date:  March, 2013
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Abstract

Protein and lipid kinases play key regulatory roles in a number of biological processes. Unsurprisingly, activating mutations in kinases have been linked to a number of disorders and diseases, most notably cancers. Thus, kinases have emerged as promising clinical targets. There are more than 500 human protein kinases and about 20 lipid kinases. Most protein kinases share a highly conserved domain, the eukaryotic protein kinase (ePK) domain, which contains the ATP and substrate‐binding sites. Many inhibitors in clinical use bind to the highly conserved ATP binding site. For this reason, many kinase inhibitors are not exclusively selective for their intended targets. Furthermore, despite the current interest in kinase inhibitors, very few kinases implicated in disease have validated inhibitors. This unit describes the human kinome, ePK structure, and types of kinase inhibitors, focusing on methods to identify potent and selective kinase inhibitors. Curr. Protoc. Pharmacol. 60:2.9.1‐2.9.14. © 2013 by John Wiley & Sons, Inc.

Keywords: kinase; small‐molecule inhibition; inhibitor selectivity; inhibitor screening; kinase domain; kinase assay

     
 
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Table of Contents

  • Introduction
  • The Kinome
  • The Architecture of Kinases
  • Types of Inhibition
  • Considerations in the Development of Kinase Inhibitors
  • Assay Formats for Measuring Kinase‐Inhibitor Interactions
  • Discussion
  • Acknowledgements
  • Literature Cited
  • Figures
     
 
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Materials

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Literature Cited

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