BAY1217389 |
| رقم الكتالوجGC19058 |
يعتبر BAY 1217389 مثبطًا قويًا وانتقائيًا للمغزل أحادي القطب 1 (MPS1) كيناز بقيمة IC 50 أقل من 10 نانومتر
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1554458-53-5
Sample solution is provided at 25 µL, 10mM.
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BAY 1217389 is a potent, and selective inhibitor of the monopolar spindle 1 (MPS1) kinase with an IC50 value less than 10 nM.
BAY 1217389 inhibits Mps1 kinase activity with IC50 value below 10 nM while showing an excellent selectivity profile. In cellular mechanistic assays BAY 1217389 abrogates nocodazole-induced SAC activity and induces premature exit from mitosis resulting in multinuclearity and tumor cell death. BAY 1217389 efficiently inhibits tumor cell proliferation in vitro[1].
BAY 1217389 achieves moderate efficacy in monotherapy in tumor xenograft studies. However, in line with its unique mode of action, when combines with paclitaxel, low doses of Mps1 inhibitor reduces paclitaxel-induced mitotic arrest in line with weakening of SAC activity. As a result, combination therapy strongly improves efficacy over paclitaxel or Mps1 inhibitor monotreatment at the respective MTDs in a broad range of xenograft models including those showing acquired or intrinsic paclitaxel-resistance. BAY 1217389 shows good tolerability without adding toxicity to paclitaxel monotherapy[1].
References:
[1]. Wengner AM, et al. Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. Mol Cancer Ther. 2016 Apr;15(4):583-92.
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Kinase experiment: |
Inhibition of recombinant human Mps1 by BAY 1161909 or BAY 1217389 is assessed in TRFRET-based in vitro kinase assays via phosphorylation of a biotinylated peptide (Biotin-Ahx-PWDPDDADITEILG-NH2). Under standard assay conditions kinase and test compound are preincubated for 15 min before enzyme reaction is started by addition of substrate and ATP upon 10 μM[1]. |
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Cell experiment: |
Cells are seeded into 96 well plates at densities ranging from 1,000 to 5,000 cells per well in the appropriate medium supplemented with 10% FCS. After 24 hours, cells are treated in quadruplicates with serial dilutions of BAY 1161909 or BAY 1217389. After further 96 hours, adherent cells are fixed with glutaraldehyde and stained with crystal violet. IC50 values are calculated by means of a 4 parameter fit[1]. |
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Animal experiment: |
Mice: For tumor xenograft studies female athymic NMRI nu/nu mice, 50 days old, average body weight 20-22 g, are used. When tumors reaches a size of approximately 20-40 mm2, depending on growth of the tumor model, animals are randomized to treatment and control groups (8-10 mice / group) and treated p.o. with vehicle (70% polyethylene glycol 400, 5% Ethanol, 25% Solutol), BAY 1161909, BAY 1217389, and/or paclitaxel. For analysis of polyploidy and multinuclearity induction in vivo, A2780cis tumor bearing female NMRI nude mice are treated with paclitaxel (i.v. once with 24 mg/kg), BAY 1161909 p.o.twice daily for 2 days with 2.5 mg/kg and in combination with paclitaxel (i.v. once 24 mg/kg) and BAY 1161909 (p.o. twice daily for 2 days 1 mg/kg)[1]. |
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References: [1]. Wengner AM, et al. Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. Mol Cancer Ther. 2016 Apr;15(4):583-92. |
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| Cas No. | 1554458-53-5 | SDF | |
| Canonical SMILES | O=C(NC1CC1)C2=CC=C(C3=CN=C4C(NCCC(F)(F)F)=CC(OC5=CC=C(OC)C(F)=C5F)=NN43)C=C2C | ||
| Formula | C27H24F5N5O3 | M.Wt | 561.5 |
| الذوبان | DMSO : ≥ 28 mg/mL (49.87 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7809 mL | 8.9047 mL | 17.8094 mL |
| 5 mM | 0.3562 mL | 1.7809 mL | 3.5619 mL |
| 10 mM | 0.1781 mL | 0.8905 mL | 1.7809 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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