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Overview
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Background
MPI-0479605 is a small-molecule inhibitor of the Mitotic Kinase Mps1 with IC50 value of 1.8nM [1].MPI-0479605 is a selective and ATP competitive inhibitor of Mps1. It shows no significant inhibition of 120 other kinases. In cells treated with nocodazole, MPI-0479605 inhibits Mps1 function through promoting the degradation of both cyclin B and securing. MPI-0479605 also suppresses the autophosphorylation of Mps1 in HEK293T cells overexpressing this enzyme. In A549 cells during mitosis, MPI-0479605 causes defects in chromosome segregation. It destroys the ability of cells to align chromosomes at the metaphase plate. Besides that, MPI-0479605-treated cells also show a significant delay or arrest in cell-cycle progression. Moreover, treatment of MPI-0479605 leads to a significant decrease in cell viability in HCT-116 cells and finally causes cell death with GI50 values ranging from 30nM to 100nM. Furthermore, MPI-0479605 shows potent antitumor effects in tumor xenograft models. MPI-0479605 at dose of 30mg/kg results in TGI of 49% in mice bearing HCT-116 xenografts [1].
[1] Tardif K D, Rogers A, Cassiano J, et al. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1. Molecular cancer therapeutics, 2011, 10(12): 2267-2275.
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