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Mps1-IN-3 Sale

目录号 : GC36651

Mps1-IN-3 是一种有效的,选择性的 MPS1 抑制剂,IC50 值为 50 nM。

Mps1-IN-3 Chemical Structure

Cas No.:1609584-72-6

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2mg
¥2,100.00
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5mg
¥3,150.00
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¥4,500.00
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¥13,500.00
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¥18,900.00
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Animal experiment:

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, 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].

References:

[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.

产品描述

Mps1-IN-3 is a potent and selective MPS1 kinase inhibitor, with an IC50 of 50 nM. 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[1].

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

Chemical Properties

Cas No. 1609584-72-6 SDF
Canonical SMILES O=S(C1=C(NC2=NC(NC3=CC=C(N4CCC(O)CC4)C=C3OC)=NC5=C2N=CN5)C=CC=C1)(C(C)C)=O
分子式 C26H31N7O4S 分子量 537.63
溶解度 Soluble in DMSO 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 1.86 mL 9.3001 mL 18.6002 mL
5 mM 0.372 mL 1.86 mL 3.72 mL
10 mM 0.186 mL 0.93 mL 1.86 mL
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Research Update

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.PMID:23940287DOI:10.1093/jnci/djt168.

Background: Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. Methods: We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3-7 mice/group). MPS1 expression levels were examined in relation to patient survival. Results: Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, Mps1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. Mps1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity. Conclusions: Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by Mps1-IN-3 sensitizing glioblastoma cells to antimitotic drugs.

Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition

Cell Death Discov 2018 Jul 16;4:12.PMID:30210815DOI:10.1038/s41420-018-0079-9.

Tumor treating fields (TTFields) are approved for glioblastoma (GBM) therapy. TTFields disrupt cell division by inhibiting spindle fiber formation. Spindle assembly checkpoint (SAC) inhibition combined with antimitotic drugs synergistically decreases glioma cell growth in cell culture and mice. We hypothesized that SAC inhibition will increase TTFields efficacy. Human GBM cells (U-87 MG, GaMG) were treated with TTFields (200 kHz, 1.7 V/cm) and/or the SAC inhibitor Mps1-IN-3 (IN-3, 4 µM). Cells were counted after 24, 48, and 72 h of treatment and at 24 and 72 h after end of treatment (EOT). Flow cytometry, immunofluorescence microscopy, Annexin-V staining and TUNEL assay were used to detect alterations in cell cycle and apoptosis after 72 h of treatment. The TTFields/IN-3 combination decreased cell proliferation after 72 h compared to either treatment alone (-78.6% vs. TTFields, P = 0.0337; -52.6% vs. IN-3, P = 0.0205), and reduced the number of viable cells (62% less than seeded). There was a significant cell cycle shift from G1 to G2/M phase (P < 0.0001). The apoptotic rate increased to 44% (TTFields 14%, P = 0.0002; IN-3 4%, P < 0.0001). Cell growth recovered 24 h after EOT with TTFields and IN-3 alone, but the combination led to further decrease by 92% at 72 h EOT if IN-3 treatment was continued (P = 0.0288). The combination of TTFields and SAC inhibition led to earlier and prolonged effects that significantly augmented the efficacy of TTFields and highlights a potential new targeted multimodal treatment for GBM.