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What general conclusions can we draw from kinase profiling data sets? | LitMetric

What general conclusions can we draw from kinase profiling data sets?

Biochim Biophys Acta

Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, DC 1930, Indianapolis, IN 46285, USA.

Published: July 2013

AI Article Synopsis

Article Abstract

Understanding general selectivity trends across the kinome has implications ranging from target selection, compound prioritization, toxicity and patient tailoring. Several recent publications have described the characterization of kinase inhibitors via large assay panels, offering a range of generalizations that influenced kinase inhibitor research trends. Since a subset of profiled inhibitors overlap across reports, we evaluated the concordance of activity results for the same compound-kinase pairs across four data sources generated from different kinase biochemical assay technologies. Overall, 77% of all results are within 3 fold or qualitatively in agreement across sources. However, the agreement for active compounds is only 37%, indicating that different profiling panels are in better agreement to determine a compound's lack of activity rather than degree of activity. Low concordance is also found when comparing the promiscuity of kinase targets evaluated from different sources, and the pharmacological similarity of kinases. In contrast, the overall promiscuity of kinase inhibitors was consistent across sources. We highlight the difficulty of drawing general conclusions from such data by showing that no significant selectivity difference distinguishes type I vs. type II inhibitors, and limited kinase space similarity that is consistent across different sources. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).

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Source
http://dx.doi.org/10.1016/j.bbapap.2012.12.023DOI Listing

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