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Monopolar spindle 1 (Mps1) inhibitors block a mitotic kinase that drives the spindle assembly checkpoint. In human cells the kinase is also known as threonine and tyrosine kinase (TTK). The MPS1 gene was first described in budding yeast, where it is needed to duplicate the spindle pole body. During mitosis Mps1 acts at unattached kinetochores and is required to recruit the checkpoint protein Mad2 to the Mad1-Mad2 core complex. Inhibition shortens mitosis and lets cells divide with misaligned chromosomes, which leads to aneuploidy. Representative compounds are AZ 3146, Mps1-IN-1, MPI-0479605 and the TTK inhibitor CFI-401870.
