| Literature DB >> 25596550 |
Edgar Jacoby1, Gary Tresadern2, Scott Bembenek3, Berthold Wroblowski2, Christophe Buyck2, Jean-Marc Neefs2, Dmitrii Rassokhin4, Alain Poncelet5, Jeremy Hunt6, Herman van Vlijmen7.
Abstract
The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the relation between hit confirmation rates and inhibitor selectivity showed unexpectedly that higher selectivity can increase the likelihood of false positives. Third, comparing the coverage of a focused to that of a random library showed that the design based on a maximum number of scaffolds was superior to a limited number of scaffolds. Therefore, selective compounds can be used in target validation, enable the jumpstarting of new kinase drug discovery projects, and chart new biological space via phenotypic screening.Mesh：
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Year: 2015 PMID： 25596550 DOI： 10.1016/j.drudis.2015.01.002
Source DB: PubMed Journal: Drug Discov Today ISSN： 1359-6446 Impact factor: 7.851