Inhibition of Nek2 by Small Molecules Affects Proteasome Activity
Figure 3
Novel Nek2 Inhibitors significantly Inhibit Nek2’s activity. (a), (b), and (c), three compounds, HCI-2184, HCI-2388, and HCI-2389 were designed by virtual screening. Synthesized compounds were validated by NMR and MS. The abilities of the three compounds to inhibit Nek2 kinase were tested by Kinase-Glo Assay. (d) HCI-2389 acts as an irreversible Nek2 inhibitor. A 0.5 hr incubation of HCI-2389 and Nek2 kinase increased the ability of HCI-2389 to inhibit Nek2. This effect was more pronounced when HCI-2389 was incubated with Nek2 kinase for 1 hr. (e) 10 nM HCI-2389 treatment for 72 hours greatly decreased the level of phosphorylated PP1-α in both Nek2 overexpressed HeLa cells and GFP controls. The effect was equal to or greater than treatment with 5 nM Nek-2 siRNA.
