Jump to main content
Jump to site search


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

Author affiliations

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

Back to tab navigation

Supplementary files

Publication details

The article was received on 20 Sep 2017, accepted on 23 Jan 2018 and first published on 23 Jan 2018


Article type: Paper
DOI: 10.1039/C7OB02344H
Citation: Org. Biomol. Chem., 2018, Advance Article
  •   Request permissions

    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, Advance Article , DOI: 10.1039/C7OB02344H

Search articles by author

Spotlight

Advertisements