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Chemoproteomic selectivity profiling of PIKK and PI3K kinase inhibitors

ABSTRACT: "Here, we report the development of a novel version of Kinobeads that extends kinome coverage to PIKK and PI3K kinases. This is achieved by inclusion of two affinity probes derived from the clinical PI3K/MTOR inhibitors Omipalisib and BGT226. The new affinity matrix was used to profile 13 clinical and pre-clinical PIKK/PI3K inhibitors. The large discrepancies between the PI3K affinity values obtained and reported results from recombinant assays led us to perform a phosphoproteomic experiment showing that the chemoproteomic assay is the better approximation of PI3K inhibitor action in-vivo."

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Maria Reinecke

LAB HEAD: Bernhard Kuster

PROVIDER: PXD011719 | Pride | 2019-03-29

REPOSITORIES: Pride

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Chemoproteomic Selectivity Profiling of PIKK and PI3K Kinase Inhibitors.

Reinecke Maria M Ruprecht Benjamin B Poser Sandra S Wiechmann Svenja S Wilhelm Mathias M Heinzlmeir Stephanie S Kuster Bernhard B Médard Guillaume G

ACS chemical biology 20190403 4

Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) have proven valuable for the elucidation of a compound's target profile under close-to-physiological conditions and often revealed potentially synergistic or toxic off-targets. Current Kinobeads enrich more than 300 native protein kinases from cell line or tissue lysates but do not systematically cover phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related kinases (PIKKs). ...[more]

PMID: 30901187

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