| Identification | Back Directory | [Name]
MPI-0479605 | [CAS]
1246529-32-7 | [Synonyms]
CS-1459
MPI-0479605
1246529-32-7
MPI0479605 HCl
MPI-0479605 USP/EP/BP
MPI-0479605;MPI 0479605;MPI0479605
N6-cyclohexyl-N2-(2-methyl-4-morpholinophenyl)-9H-purine-2,6-diamine
N6-Cyclohexyl-N2-[2-methyl-4-(4-morpholinyl)phenyl]-9H-purine-2,6-diamine
9H-?Purine-?2,?6-?diamine, N6-?cyclohexyl-?N2-?[2-?methyl-?4-?(4-?morpholinyl)?phenyl]?- | [Molecular Formula]
C22H29N7O | [MDL Number]
MFCD28099811 | [MOL File]
1246529-32-7.mol | [Molecular Weight]
407.52 |
| Chemical Properties | Back Directory | [Boiling point ]
745.8±70.0 °C(Predicted) | [density ]
1.318±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | [solubility ]
Soluble in DMSO | [form ]
A crystalline solid | [pka]
10.52±0.10(Predicted) | [color ]
White to gray |
| Hazard Information | Back Directory | [Description]
MPI-0479605 is a potent and ATP-competitive inhibitor of the mitotic kinase MPS1 (IC50 = 1.8 nM). It is selective for MPS1 over a panel of 79 kinases at a concentration of 500 nM. MPI-0479605 induces time-dependent degradation of cyclin B and securin and decreases phosphorylation of BUBR1 resulting in failed cytokinesis in HeLa cells arrested by nocodazole . It also causes misalignment of chromosomes at the anaphase plate and aneuploidy in A549 cells and slows cell cycle progression of HCT116 and COLO 205 cells irrespective of p53 activity. MPI-0479605 (30-150 mg/kg) reduces tumor volume in an HCT116 mouse colon cancer xenograft model in a dose-dependent manner. | [Uses]
MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM. | [Synthesis]
The general procedure for the synthesis of N6-cyclohexyl-N2-(2-methyl-4-morpholinophenyl)-9H-purine-2,6-diamine from compound (CAS:39639-45-7) and compound (CAS:1246532-35-3) was as follows: compound 1 (2.00 g, 7.91 mmol) was mixed with compound 4 (2.53 g, 9.56 mmol), sodium acetate (980 mg, 11.95 mmol) and chloroform (40 mL) in an 80 mL microwave reaction flask to form a suspension. Subsequently, the mixture was heated to 150 °C in a microwave reactor and maintained for 30 min. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The resulting crude product was purified by reversed-phase medium pressure liquid chromatography (MPLC) to give a final white solid product in 12-30% yield. | [in vivo]
MPI-0479605 (30 mg/kg daily or 150 mg/kg every fourth day (Q4D), i.p.) inhibits tumor growth by 49% and 74 % in HCT-116 xenografts. However, MPI-0479605 does not show inhibitory activity via daily dosing on the Colo-205 xenografts, and dosing every four days causes 63% tumor growth inhibition (TGI)[1]. | [IC 50]
Mps1: 1.8 nM (IC50); ALK: 0.26 μM (IC50); B-RAF: 3.2 μM (IC50); ERK2: 3.9 μM (IC50); FAK1: 2.7 μM (IC50); FER: 0.59 μM (IC50); FLT3: 0.08 μM (IC50); INSR: 0.38 μM (IC50); JNK1: 0.11 μM (IC50); PLK4: 3.3 μM (IC50); STK33: 1.1 μM (IC50) | [storage]
Store at -20°C | [References]
[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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