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Determining MELK inhibitor specificity using MIB/MS

ABSTRACT: The key objectives of this study were to evaluate the selectivity profiles of three MELK inhibitors, 8a, HTH, and OTS, using a cell-based assay, in order to identify a highly selective inhibitor to subsequently investigate MELK function. To this end, we utilized a chemical proteomics approach called multiplexed kinase inhibitor beads/mass spectrometry (MIB/MS) to characterize the selectivity of these MELK inhibitors in TNBC cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Laura Herring

LAB HEAD: Lee M. Graves

PROVIDER: PXD016022 | Pride | 2020-01-09

REPOSITORIES: Pride

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Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells.

McDonald Ian M IM Grant Gavin D GD East Michael P MP Gilbert Thomas S K TSK Wilkerson Emily M EM Goldfarb Dennis D Beri Joshua J Herring Laura E LE Vaziri Cyrus C Cook Jeanette Gowen JG Emanuele Michael J MJ Graves Lee M LM

The Journal of biological chemistry 20200102 8

The maternal embryonic leucine zipper kinase (MELK) has been implicated in the regulation of cancer cell proliferation. RNAi-mediated MELK depletion impairs growth and causes G<sub>2</sub>/M arrest in numerous cancers, but the mechanisms underlying these effects are poorly understood. Furthermore, the MELK inhibitor OTSSP167 has recently been shown to have poor selectivity for MELK, complicating the use of this inhibitor as a tool compound to investigate MELK function. Here, using a cell-based p ...[more]

PMID: 31896573

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