Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors. Issue 9 (7th February 2018)

• Record Type: Journal Article
• Authors: Zhou, Shu; Li, Guo-Bo; Luo, Lin; Zhong, Lei; Chen, Kai; Li, Hui; Jiang, Xiao-Juan; Fu, Qi; Long, Xin; Bao, Jin-ku
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 9(2018)
• Page Start: 1489
• Page End: 1495
• Publication Date: 2018-02-07
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02344h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The new MELK inhibitor16 showed no inhibitory effect on cancer growth, but can suppress the phosphorylation of focal adhesion kinase, a key kinase in regulating cancer cell migration and invasion. 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 compounds4 and16 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 that16 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 that16 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.