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CFI-402257

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Chemical Structure| 1610759-22-2 同义名 : -
CAS号 : 1610759-22-2
货号 : A104594
分子式 : C28H30N6O3
纯度 : 98%
分子量 : 498.576
MDL号 : MFCD31382135
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Monopolar spindle 1 (Mps1/TTK) kinase is a key component of the spindle assembly checkpoint (SAC), which is essential for cell survival. CFI-402257 is orally bioavailable, highly selective inhibitor of Mps1 with an IC50 value of 1.2 ± 0.4 nM and is ATP competitive with a Ki value of 0.09 ± 0.02 nM. In cells exogenously expressing human Mps1, CFI-402257 blocked auto-phosphorylation of Mps1 at threonine 12/serine 15 with an EC50 value of 6.5 ± 0.5 nM. CFI-402257 also exerts inhibitory activity on the activation of the SAC with an IC50 value of 64 ± 5 nM. Treatment of HCT116 cells with 200 nM CFI-402257 led to a remarkable increase in chromosome missegregations compared to DMSO-treated control cells. CFI-402257 at 50 - 3000 nM increased the frequency of HCT116 cells with an aneuploid DNA content, and the massive aneuploidy was observed when cells were dosed with 100 nM CFI-402257. Moreover, CFI-402257 exhibited potent growth inhibitory effect on a vast majority of human cancer cell lines with a median IC50 value of 15 nM. In a mouse xenografted model of MDA-MB-231 human TNBC cells, daily oral administration of CFI-402257 at 5 mg/kg and 6 mg/kg for 22 days showed tumor growth inhibition (TGI) of 74% and 89%, respectively. Similar results were found in mice xenografted with MDA-MB-468 human TNBC cells (5 mg/kg, TGI = 75%; 6 mg/kg, TGI = 94%). In addition, significantly decreased number of phospho-histone H3 serine 10-positive cells per square millimeter of tumor tissue was observed in CFI-402257-treated tumors (6 mg/kg and 35 mg/kg) as compared to vehicle controls[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.01mL

0.40mL

0.20mL

10.03mL

2.01mL

1.00mL

20.06mL

4.01mL

2.01mL
参考文献

[1]Mason JM, Wei X, et al. Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132.

[2]Liu Y, Laufer R, et al. Discovery of Pyrazolo[1,5-a] pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent. ACS Med Chem Lett. 2016 May 6;7(7):671-5.

[3]Mason JM, Wei X, Fletcher GC, Kiarash R, Brokx R, Hodgson R, Beletskaya I, Bray MR, Mak TW. Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132. doi: 10.1073/pnas.1700234114. Epub 2017 Mar 7. PMID: 28270606; PMCID: PMC5373378.