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    InvivoChem Cat #: V1630
    CAS #: 1246529-32-7Purity ≥98%

    Description: MPI-0479605 (MPI0479605; MPI 0479605) is an ATP-competitive and selective inhibitor of mitotic kinase Mps1 (Monopolar spindle1) with potential antineoplastic activity. It inhibits Mps1 with an IC50 of 1.8 nM, and shows >40-fold selectivity over other closely related kinases. 

    References: Mol Cancer Ther. 2011 Dec;10(12):2267-75.

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    Molecular Weight (MW)407.51
    CAS No.1246529-32-7
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 62 mg/mL (152.1 mM)
    Water:<1 mg/mL
    Ethanol: 2 mg/mL (4.9 mM)
    Other info

    Chemical Name: N6-cyclohexyl-N2-(2-methyl-4-morpholinophenyl)-9H-purine-2,6-diamine


    InChi Code: InChI=1S/C22H29N7O/c1-15-13-17(29-9-11-30-12-10-29)7-8-18(15)26-22-27-20-19(23-14-24-20)21(28-22)25-16-5-3-2-4-6-16/h7-8,13-14,16H,2-6,9-12H2,1H3,(H3,23,24,25,26,27,28)

    SMILES Code: CC1=CC(N2CCOCC2)=CC=C1NC3=NC(NC4CCCCC4)=C5N=CNC5=N3           


    MPI0479605; MPI 0479605; MPI-0479605

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    In Vitro

    In vitro activity: MPI-0479605 impairs the SAC and the bipolar attachment of chromosomes to the mitotic spindle, which results in chromosome segregation defects and aneuploidy. MPI-0479605 results in a significant decrease in cell viability with GI50 ranging from 30 to 100 nM in a panel of tumor cell lines. In addition, MPI-0479605 also causes cell growth arrest and ultimately promotes cell death by apoptosis or mitotic catastrophe.

    Kinase Assay: To measure Mps1 activity, 25 ng of recombinant, full-length enzyme is incubated in reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.01% Triton X-100 and 5 μM Myelin basic protein (MBP)) containing vehicle (DMSO alone) or inhibitors. Forty μM ATP (2xKm) is added with 1 μCi [γ-33P]ATP and the reaction is incubated at room temperature for 45 minutes. Reactions are terminated with 3% phosphoric acid and transferred to P81 filter plates. Samples are washed in 1% phosphoric acid and 33P radioactivity is measured on a TopCount scintillation reader. In-house kinase assays are all carried out at 2xKm ATP concentrations. MPI-0479605 (500 nM) is also screened against a larger kinase panel.

    Cell Assay: Cells (A549, Colo205, DU-4475, DU-145, HCC827, HCT116, HT29, MDA MB 231, MiaPaCa2, NCI-H69, NCI-H460, NCI-N87, OPM2, and OVCAR-3 cells.) are treated for 3 or 7 days with various concentrations of MPI-0479605 and the GI50 is determined. Cell viability is measured with CellTiter-Glo.

    In VivoMPI-0479605 (30 mg/kg daily or 150 mg/kg every 4 days, i.p.) shows antitumor activity in colon cancer xenograft models.
    Animal modelMice bearing subcutaneous HCT-116 or Colo-205 human tumor cell xenografts.
    Formulation & DosageDissolved in 5% dimethylacetamide (DMA)/12% ethanol/40% PEG-300; daily with 30 mg/kg or every 4 days with 150 mg/kg; i.p. injection 

    Mol Cancer Ther. 2011 Dec;10(12):2267-75.

    These protocols are for reference only. InvivoChem does not independently validate these methods.





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