Hijacking monopolar spindle 1 (MPS1) for various cancer types by small molecular inhibitors: Deep insights from a decade of research and patents.

ABSTRACT

Monopolar spindle 1 (MPS1) has garnered significant attention due to its pivotal role in regulating the cell cycle. Anomalous expression and hyperactivation of MPS1 have been associated with the onset and advancement of diverse cancers, positioning it as a promising target for therapeutic interventions. This review focuses on MPS1 small molecule inhibitors from the past decade, exploring design strategies, structure-activity relationships (SAR), safety considerations, and clinical performance. Notably, we propose prospects for MPS1 degraders based on proteolysis targeting chimeras (PROTACs), as well as reversible covalent bonding as innovative MPS1 inhibitor design strategies. The objective is to provide valuable information for future development and novel perspectives on potential MPS1 inhibitors.