MPI-0479605

• CAT Number: I000979
• CAS Number: 1246529-32-7
• Molecular Formula: C₂₂H₂₉N₇O
• Molecular Weight: 407.51
• Purity: ≥95%
• Target: Kinesin
• Solubility: DMSO: ≥ 11 mg/mL
• Storage: Store at -20°C
• IC50: 1.8 nM
• InChI: 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)
• InChIKey: OVJBNYKNHXJGSA-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)N2CCOCC2)NC3=NC4=C(C(=N3)NC5CCCCC5)NC=N4

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.IC50 value: 1.8 nMTarget: Mps 1in vitro: 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.in vivo: MPI-0479605 (30 mg/kg daily or 150 mg/kg every 4 days, i.p.) exhibits antitumor activity in colon cancer xenograft models.

Reference

1:Mol Cancer Ther. 2011 Dec;10(12):2267-75. doi: 10.1158/1535-7163.MCT-11-0453. Epub 2011 Oct 6. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1.Tardif KD,Rogers A,Cassiano J,Roth BL,Cimbora DM,McKinnon R,Peterson A,Douce TB,Robinson R,Dorweiler I,Davis T,Hess MA,Ostanin K,Papac DI,Baichwal V,McAlexander I,Willardsen JA,Saunders M,Christophe H,Kumar DV,Wettstein DA,Carlson RO,Williams BL, PMID: 21980130 DOI: 10.1158/1535-7163.MCT-11-0453 Abstract: Mps1 is a dual specificity protein kinase that is essential for the bipolar attachment of chromosomes to the mitotic spindle and for maintaining the spindle assembly checkpoint until all chromosomes are properly attached. Mps1 is expressed at high levels during mitosis and is abundantly expressed in cancer cells. Disruption of Mps1 function induces aneuploidy and cell death. We report the identification of MPI-0479605, a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.