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

Eur J Med Chem. 2024 Jul 5:273:116504. doi: 10.1016/j.ejmech.2024.116504.

Chengyuan Liang ¹, Ying Zhou ², Liang Xin ², Kairui Kang ², Lei Tian ³, Dezhu Zhang ⁴, Han Li ⁵, Qianqian Zhao ², Hong Gao ⁶, Zhenfeng Shi ⁷

Affiliations

1 School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi'an, 710021, China; Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an, 710021, China. Electronic address: [email protected].
2 School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi'an, 710021, China; Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an, 710021, China.
3 Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an, 710021, China; College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science& Technology, Xi'an, 710021, China.
4 Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an, 710021, China; Shaanxi Panlong Pharmaceutical Group Co., Ltd., Xi'an, 710025, China.
5 School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi'an, 710021, China; Shaanxi Pioneer Biotech Co., Ltd., Xi'an, 710082, China.
6 Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an, 710021, China; Shaanxi Pioneer Biotech Co., Ltd., Xi'an, 710082, China.
7 Department of Urology Surgery Center, The People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, 830002, China.

PMID: 38795520 DOI: 10.1016/j.ejmech.2024.116504

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.

Keywords

Monopolar spindle 1 (MPS1) inhibitors; Proteolysis targeting chimaeras (PROTACs); Structure-activity relationships (SAR).

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