Abstract
The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec® and the recent clinical approval of a number of small molecule drugs that target protein kinases have intensified the search for novel protein kinase inhibitors. Since most small molecule kinase inhibitors target the highly conserved ATP-binding pocket of this enzyme family, the target selectivity of these molecules is a major concern. Due to the large size of the human kinome, it is a formidable challenge to determine the absolute specificity of a given protein kinase inhibitor, but recent technological developments have made substantial progress in achieving this goal. This review summarizes some of the most recent experimental techniques that have been developed for the determination of protein kinase inhibitor selectivity. Special emphasis is placed on the results of these screens and the general insights that they provide into kinase inhibitor target selectivity.
Keywords: ATP-binding cleft, mitogen activated protein kinase kinase, Affinity chromatography, Purvalanol B, yeast 2-hybrid assay
Combinatorial Chemistry & High Throughput Screening
Title: Chemical Genomic and Proteomic Methods for Determining Kinase Inhibitor Selectivity
Volume: 10 Issue: 8
Author(s): Ratika Krishnamurty and Dustin J. Maly
Affiliation:
Keywords: ATP-binding cleft, mitogen activated protein kinase kinase, Affinity chromatography, Purvalanol B, yeast 2-hybrid assay
Abstract: The clinical success of the Bcr-Abl tyrosine kinase inhibitor Gleevec® and the recent clinical approval of a number of small molecule drugs that target protein kinases have intensified the search for novel protein kinase inhibitors. Since most small molecule kinase inhibitors target the highly conserved ATP-binding pocket of this enzyme family, the target selectivity of these molecules is a major concern. Due to the large size of the human kinome, it is a formidable challenge to determine the absolute specificity of a given protein kinase inhibitor, but recent technological developments have made substantial progress in achieving this goal. This review summarizes some of the most recent experimental techniques that have been developed for the determination of protein kinase inhibitor selectivity. Special emphasis is placed on the results of these screens and the general insights that they provide into kinase inhibitor target selectivity.
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Cite this article as:
Krishnamurty Ratika and Maly J. Dustin, Chemical Genomic and Proteomic Methods for Determining Kinase Inhibitor Selectivity, Combinatorial Chemistry & High Throughput Screening 2007; 10 (8) . https://dx.doi.org/10.2174/138620707782507368
DOI https://dx.doi.org/10.2174/138620707782507368 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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