Comprehensive characterization of the Published Kinase Inhibitor Set View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-01

AUTHORS

Jonathan M Elkins, Vita Fedele, Marta Szklarz, Kamal R Abdul Azeez, Eidarus Salah, Jowita Mikolajczyk, Sergei Romanov, Nikolai Sepetov, Xi-Ping Huang, Bryan L Roth, Ayman Al Haj Zen, Denis Fourches, Eugene Muratov, Alex Tropsha, Joel Morris, Beverly A Teicher, Mark Kunkel, Eric Polley, Karen E Lackey, Francis L Atkinson, John P Overington, Paul Bamborough, Susanne Müller, Daniel J Price, Timothy M Willson, David H Drewry, Stefan Knapp, William J Zuercher

ABSTRACT

Despite the success of protein kinase inhibitors as approved therapeutics, drug discovery has focused on a small subset of kinase targets. Here we provide a thorough characterization of the Published Kinase Inhibitor Set (PKIS), a set of 367 small-molecule ATP-competitive kinase inhibitors that was recently made freely available with the aim of expanding research in this field and as an experiment in open-source target validation. We screen the set in activity assays with 224 recombinant kinases and 24 G protein-coupled receptors and in cellular assays of cancer cell proliferation and angiogenesis. We identify chemical starting points for designing new chemical probes of orphan kinases and illustrate the utility of these leads by developing a selective inhibitor for the previously untargeted kinases LOK and SLK. Our cellular screens reveal compounds that modulate cancer cell growth and angiogenesis in vitro. These reagents and associated data illustrate an efficient way forward to increasing understanding of the historically untargeted kinome. More... »

PAGES

95-103

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.3374

    DOI

    http://dx.doi.org/10.1038/nbt.3374

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1024715377

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26501955


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