BAY 1217389 is an effective and selective inhibitor of the monopolar spindle 1 (MPS1) kinase (IC50<10 nM).

Mps1:<10 nM

在生化测定中，BAY 1217389的IC50值为0.63±0.27 nmol/L，对其他激酶表现出高选择性，且发现能够结合到PDGFRβ（<10 nmol/L）、Kit（10至100 nmol/L之间）、CLK1、CLK2、CLK4、JNK1、JNK2、JNK3、LATS1、MAK、MAPKAP2、MERTK、p38β、PDGFRα、PIP5K1C、PRKD1及RPS6KA5（100至1,000 nmol/L之间）。在细胞机制测定中，BAY1217389能够阻断诺考达唑诱导的SAC活性并诱导细胞提前退出有丝分裂（“有丝分裂突破”），导致多核性和肿瘤细胞死亡。研究发现，它能够抑制细胞增殖，中位IC50为6.7 nmol/L（范围为3至>300 nmol/L）。

在体内实验中，BAY 1217389以单药治疗方式在肿瘤异种移植研究中取得了中等疗效。在所测试的物种中，其血液清除率低。Vss较高，末端半衰期较长。BAY 1217389通过口服给予雌性NMRI小鼠（1 mg/kg）和雄性Wistar大鼠（0.5 mg/kg）。血浆峰值浓度在1.5至7小时之间观察到。在大鼠中口服生物利用度高，而在小鼠中为中等[1]。

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].

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 compounds. 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 using the company's own software.(Only for Reference)