TTK protein kinase (MPS1) (TTK)

TTK protein kinase, also known as Monopolar spindle 1 (MPS1), is a dual-specificity kinase that serves as a master regulator of the spindle assembly checkpoint (SAC) during mitosis (Source: Wikipedia, UniProt). It is essential for ensuring that chromosomes are properly aligned and attached to the mitotic spindle before the cell proceeds to anaphase (Source: NIH). In many human cancers, including breast, lung, and gastric tumors, TTK is significantly overexpressed, which correlates with poor prognosis and increased chromosomal instability (Source: GeneCards, NIH). Because cancer cells often rely on the SAC to manage their aneuploid genomes, TTK has emerged as a high-priority therapeutic target (Source: ResearchGate). Small-molecule inhibitors of TTK, such as empesertib and CFI-402257, work by blocking its kinase activity, thereby overriding the SAC and inducing massive chromosome missegregation (Source: ACS Publications). This process leads to mitotic catastrophe and apoptosis, specifically targeting rapidly dividing malignant cells (Source: NIH). Clinical development of these inhibitors is supported by biomarkers like TP53 mutation status and 1q21 amplification, which may predict sensitivity to treatment (Source: Haematologica). However, challenges such as the development of resistance mutations in the ATP-binding pocket and potential off-target toxicities must be managed in clinical settings (Source: NIH).

Other names

Monopolar spindle 1 kinaseMPS1MPS1L1CT96MPH1ESKPYTPhosphotyrosine picked threonine-protein kinaseDual specificity protein kinase TTK

TTK/MPS1 inhibitors bind to the ATP-binding pocket of the kinase, blocking its activity and abrogating the spindle assembly checkpoint (SAC). This leads to premature mitotic exit, chromosome missegregation, and mitotic catastrophe (Source: ACS Publications, NIH).