product name MPI-0479605
Description: MPI-0479605 is a potent, ATP competitive and selective inhibitor of mitotic kinase Mps1 with IC50 of 1.8 nM, >40-fold selectivity over other kinases. In vitro assay, cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.
References: Mol Cancer Ther. 2011 Dec;10(12):2267-75.
407.51
Formula
C22H29N7O
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)
Solubility (In vivo)
Synonyms
other peoduct :
| 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 Vivo | MPI-0479605 (30 mg/kg daily or 150 mg/kg every 4 days, i.p.) shows antitumor activity in colon cancer xenograft models. |
| Animal model | Mice bearing subcutaneous HCT-116 or Colo-205 human tumor cell xenografts. |
| Formulation & Dosage | Dissolved 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 |
| References | Mol Cancer Ther. 2011 Dec;10(12):2267-75. |
