Lima Inês, Borges Fernanda, Pombinho António, Chavarria Daniel
CIQUP-IMS - Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre s/n, 4169-007 Porto, Portugal.
i3S, Institute for Research and Innovation in Health, University of Porto 4200-135 Porto, Portugal; IBMC, Institute for Molecular and Cell Biology, University of Porto 4200-135 Porto, Portugal.
Drug Discov Today. 2025 May;30(5):104355. doi: 10.1016/j.drudis.2025.104355. Epub 2025 Apr 10.
The spindle assembly checkpoint (SAC) is a surveillance mechanism required for the fidelity of chromosome segregation, ensuring that anaphase is not initiated until all chromosomes are properly attached to the mitotic spindle. In cancer cells, SAC inactivation leads to aneuploidy beyond the cell's adaptation, culminating in cell death. This review provides a concise overview of the SAC signaling process and properties. Recent drug discovery strategies to selectively target kinases, particularly Aurora B and monopolar spindle kinase (MPS1), aimed at developing innovative anticancer agents able to override SAC are also presented.
纺锤体组装检查点（SAC）是确保染色体分离准确性的一种监测机制，可确保在所有染色体正确附着于有丝分裂纺锤体之前不会启动后期。在癌细胞中，SAC失活会导致非整倍性超出细胞的适应能力，最终导致细胞死亡。本综述简要概述了SAC信号传导过程及其特性。还介绍了最近旨在开发能够克服SAC的创新抗癌药物的选择性靶向激酶，特别是极光激酶B和单极纺锤体激酶（MPS1）的药物发现策略。
