MPI-0479605

MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM.

Signaling Pathways >> Cell Cycle/DNA Damage >> Mps1

Signaling Pathways >> Cytoskeleton >> Mps1

Research Areas >> Cancer

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)

MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM. MPI-0479605 (0.1-10 μM) reduces cell viability of HCT-116 cells in a dose-dependent manner. MPI-0479605 shows severe defects in the ability to align chromosomes at the metaphase plate, but causes complete cytokinesis[1].

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].

HCT-116 or Colo-205 cells are transplanted subcutaneously into the flanks of nude (nu+/nu+) mice and compound (MPI-0479605) treatment is initiated when tumor masses reaches an average size of 100 mm3. MPI-0479605 is formulated in 5% dimethylacetamide (DMA)/12% ethanol/40% PEG-300, ispinesib is formulated in 2% cremaphor/2% DMA, and 5-fluorouracil is formulated in 2% sodium bicarbonate. Tumor volume is measured using vernier calipers and tumor growth inhibition (TGI) is calculated as: %TGI= 100-100(change in median tumor volume of treated)/(change in median tumor volume control)[1].

[1]. Tardif KD, et al. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1. Mol Cancer Ther. 2011 Dec;10(12):2267-2275.

CFI402257 | BAY1217389 | BAY 1161909 | NMS-P715 | AZ 3146 | BOS172722 | Mps1-IN-1 | Mps1-IN-2 | Mps1-IN-3 | CCT251455