WDR51B Inhibitors

Chemical inhibitors of WDR51B can disrupt its role in various stages of cell division by targeting specific proteins involved in the cell cycle and mitosis. Palbociclib, Roscovitine, Dinaciclib, and Purvalanol A inhibit cyclin-dependent kinases (CDKs) such as CDK1, CDK2, CDK4, and CDK6, which are vital for the progression of the cell cycle. By inhibiting these kinases, these chemicals block the phosphorylation of proteins like the retinoblastoma (Rb) protein, leading to cell cycle arrest. Since WDR51B is implicated in cell division, particularly in centriole duplication, its function is inhibited as a consequence of the cell cycle arrest. Similarly, Nocodazole and Taxol target microtubules, which are structural components essential for mitotic spindle function. Nocodazole disrupts microtubule polymerization, while Taxol stabilizes microtubules to such an extent that it prevents their dynamic instability, both leading to the inhibition of WDR51B's role in spindle assembly and centrosome separation.

In addition to targeting the cell cycle, other chemical inhibitors affect mitotic kinases and proteins involved in spindle assembly. BI 2536 and Alisertib inhibit polo-like kinase 1 (PLK1) and Aurora A kinase, respectively, both of which are crucial for mitosis. The inhibition of PLK1 and Aurora A kinase results in mitotic arrest and disruption of centrosome maturation and separation, processes in which WDR51B has functional roles. S-Trityl-L-cysteine and Monastrol are specific inhibitors of the mitotic kinesin Eg5, leading to spindle bipolarity defects, which also functionally inhibit WDR51B. Moreover, ZM447439, an inhibitor of Aurora kinases, compromises spindle assembly and cytokinesis, further inhibiting WDR51B's role in these processes. Mardepodect, which inhibits the microtubule depolymerizing kinesin MCAK, affects chromosome segregation and spindle dynamics, implicating the functional inhibition of WDR51B in these mitotic events. Collectively, these chemical inhibitors can directly or indirectly disrupt the functional role of WDR51B in cell cycle progression and mitosis by targeting various proteins and processes essential for cell division.