Ska1 Inhibitors

Ska1 inhibitors function primarily by perturbing the molecular interactions and signaling cascades that Ska1 engages in during cell division. Microtubule-interacting compounds such as Taxol, Vinblastine, and Colchicine directly impact Ska1's essential role in microtubule-kinetochore attachment and spindle assembly. Taxol stabilizes microtubules, the dynamic instability necessary for Ska1 to effectively anchor kinetochores. Conversely, Vinblastine and Colchicine destabilize microtubules, hindering Ska1's ability to form proper connections between kinetochores and microtubules. Nocodazole and Paclitaxel operate in a similar vein by perturbing microtubule dynamics, further disabling Ska1's functional role in these structures.

Kinase inhibitors provide another angle for Ska1 inhibition. Polo-like kinase 1 (PLK1) is crucial for various phosphorylation events that modulate Ska1 function. PLK1 Inhibitors like BI2536 compromise these events, leading to altered Ska1 activity. Aurora A and Aurora B inhibitors specifically target kinases that phosphorylate Ska1, which is essential for proper kinetochore-microtubule attachment and error correction during metaphase. The cyclin-dependent kinase 1 (CDK1) inhibitor disrupts cell cycle processes, altering Ska1's function in the division cycle. Finally, compounds like ZM447439, Hesperadin, and AZ3146 exert their influence by targeting kinases essential for Ska1's role in spindle assembly and checkpoints, thereby affecting its functionality in a targeted manner.