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MPS1-IN-3 is a small molecule inhibitor of Monopolar spindle 1 (MPS1), also known as TTK protein kinase. MPS1 is a dual-specificity kinase that serves as a master regulator of the spindle assembly checkpoint (SAC), a critical surveillance mechanism that ensures accurate chromosome segregation during mitosis by delaying anaphase until all chromosomes are properly attached to the spindle microtubules. By inhibiting MPS1, MPS1-IN-3 causes cells to bypass the SAC, leading to premature mitotic exit, severe aneuploidy, and subsequent apoptosis. Research has demonstrated that MPS1-IN-3 can significantly enhance the efficacy of Tumor Treating Fields (TTFields) in glioblastoma models, suggesting that combining physical disruption of the mitotic spindle with chemical inhibition of the mitotic checkpoint may provide a synergistic therapeutic effect.
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