Nek2 Inhibitors

Nek2 inhibitors encompass a range of compounds designed to interfere with the function or regulation of Nek2, a serine/threonine kinase implicated in the control of centrosome separation and spindle assembly during the cell cycle. These inhibitors work either by direct inhibition of the kinase's active site or through indirect mechanisms affecting the cell cycle and mitotic kinase networks that Nek2 is part of. For instance, CDK inhibitors such as SU9516 and Purvalanol A lead to a halt in cell cycle progression, which is a necessary precursor for Nek2 activation and function. As Nek2 activity is synchronized with cell cycle phases, particularly the G2/M transition, inhibition of CDKs can hinder the appropriate localization and activity of Nek2 during mitosis. Beyond cell cycle arrest, other inhibitors target kinases that phosphorylate proteins within the centrosome and mitotic spindle assembly pathways. Inhibitors like tozasertib and alisertib block Aurora kinases, blocking the phosphorylation and activation of Nek2 or its substrate proteins. This disruption affects centrosome duplication and spindle formation, central processes in cell division where Nek2 has essential roles. Compounds such as S-trityl-L-cysteine and volasertib target other mitotic kinases like Eg5 and Plk1, respectively. These kinases are pivotal in maintaining the fidelity of mitosis, and their inhibition can indirectly influence Nek2 by destabilizing the structures it regulates. Collectively, these Nek2 inhibitors provide critical tools for dissecting the molecular choreography of cell division and the specific contributions of Nek2 within this vital cellular process.