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Issue 9, 2018
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Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors

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Abstract

Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and plays a key functional role in various cancer cells. Although MELK may not be a cancer addiction target, the development of specific MELK inhibitors would provide useful chemical tools for synthetic lethal investigation. Herein, we identified several hit compounds using a customized structure-based virtual screening, among which compounds 4 and 16 showed the most potent inhibition to MELK with IC50 values of 3.52 μM and 178.3 nM, respectively. In vitro cell-based assays revealed that 16 has no effect on the growth of various types of cancer cells, but has the potential to inhibit cancer cell migration and invasion. Western blotting analyses revealed that 16 suppresses the phosphorylation of focal adhesion kinase (FAK), a downstream molecule of MELK, which is a key kinase in regulating cancer cell migration and invasion.

Graphical abstract: Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors

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Supplementary files

Article information


Submitted
20 Sep 2017
Accepted
23 Jan 2018
First published
23 Jan 2018

Org. Biomol. Chem., 2018,16, 1489-1495
Article type
Paper

Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors

S. Zhou, G. Li, L. Luo, L. Zhong, K. Chen, H. Li, X. Jiang, Q. Fu, X. Long and J. Bao, Org. Biomol. Chem., 2018, 16, 1489
DOI: 10.1039/C7OB02344H

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