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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

561.50

C₂₇H₂₄F₅N₅O₃

1554458-53-5

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL (178.09 mM)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: 2.5 mg/mL (4.45 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (4.45 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (4.45 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.45 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Wengner AM, et al. Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. Mol Cancer Ther. 2016 Apr;15(4):583-92.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Wengner AM, et al. Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. Mol Cancer Ther. 2016 Apr;15(4):583-92.