Preclinical activity of MBM-5 in gastrointestinal cancer by inhibiting NEK2 kinase activity.

ABSTRACT: NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner. This inhibition impeded mitotic progression by inducing chromosome segregation defects and cytokinesis failure; therefore leading to accumulation o

SUBMITTER: Fang Y 

PROVIDER: S-EPMC5346717 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature