MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a 
mitotic mechanism specifically required for proper chromosomal alignment and 
segregation. It has been found aberrantly overexpressed in a wide range of human 
tumors and is necessary for tumoral cell proliferation. Here we report the 
identification and characterization of NMS-P715, a selective and orally 
bioavailable MPS1 small-molecule inhibitor, which selectively reduces cancer 
cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates 
mitosis and affects kinetochore components localization causing massive 
aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor 
growth in preclinical cancer models. Inhibiting the SAC could represent a 
promising new approach to selectively target cancer cells.