MPI-0479605 is a potent, selective, ATP competitive inhibitor of Mps1 with IC50 of 1.8 nM.
MPI-0479605 triggers the time-dependent degradation of both cyclin B and securin, decreases BubR1 phosphorylation in nocodazole-arrested cells, blocks apparent autophosphorylation of Mps1 at threonine 676 in HEK293T cells.
MPI-0479605 impairs spindle assembly checkpoint (SAC), resulting in chromosome segregation defects and aneuploidy, induces p53-p21 pathway in an ATM- and ATR-dependent manner.
MPI-0479605 exhibits cytotoxicity across a broad range of tumor cell lines and antitumor activity in human tumor xenografts.
