Mps1-IN-3

Mps1-IN-3 is a potent and selective MPS1 kinase inhibitor, with an IC50 of 50 nM.

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

Signaling Pathways >> Cytoskeleton >> Mps1

Research Areas >> Cancer

Mps1:50 nM (IC50)

Mps1-IN-3 is a potent MPS1 kinase inhibitor, with an IC50 of 50 nM. Mps1-IN-3 inhibits the proliferation of U251 glioblastoma cells with an IC50 of appr 5 µM. Mps1-IN-3 (2 μM) can completely abrogates checkpoint. Furthermore, Mps1-IN-3 (5 μM) sensitizes all glioblastoma cells (U251, U87, VU147 and GBM8) to 3 nM of vincristine[1].

Mps1-IN-3 (2 mg/kg, i.v.) sensitizes glioblastoma cells to vincristine in murine tumor models, with prolonged survival and no toxicity[1].

Mice[1] Six-week old athymic female nude mice weighing about 25 g are stereotactically injected with 1 × 106 U251-FM-shCTRL or shMPS1 cells, or U251-FM, or 3 × 105 GBM8-FM cells (in 10 and 4 μL PBS, respectively) using a stereotactic instrument after drilling a small hole in the cranium of the mice. For the U251-FM-shRNA experiment, a minimum of 3 mice per group is used, and for the U251-FM and GBM8-FM cells, at least 5 mice per group are used. Tumor growth is monitored by Fluc bioluminescence imaging after injection of 150 μL D-luciferin (50 mg/mL) and imaging 10 min later for luciferase-mediated photon activity using the IVIS Lumina imaging system for the U251-FM model and the IVIS Spectrum for the GBM8-FM model. When tumors reach a size around 107 radiance for the U251 model and 5 × 105 radiance for the GBM8 model, mice are intravenously injected with vehicle, 0.5 mg/kg body weight vincristine in DMSO, and/or 2 mg/kg MPS1-IN-3 in 20% hydroxypropyl-beta-cyclodextrin (HPbetaCD), twice/week over three weeks. Tumor volume is monitored weekly by Fluc imaging[1].

[1]. Tannous BA, et al. Effects of the selective MPS1 inhibitor MPS1-IN-3 on glioblastoma sensitivity to antimitotic drugs. J Natl Cancer Inst. 2013 Sep 4;105(17):1322-31.

CFI402257 | BAY1217389 | BAY 1161909 | NMS-P715 | AZ 3146 | BOS172722 | MPI-0479605 | Mps1-IN-1 | Mps1-IN-2 | CCT251455