产品说明书

CYC-116

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Chemical Structure| 693228-63-6 同义名 : -
CAS号 : 693228-63-6
货号 : A199103
分子式 : C18H20N6OS
纯度 : 99%+
分子量 : 368.456
MDL号 : MFCD14155805
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 14 mg/mL(38 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+water 0.1 mg/mL clear

PO 0.5% CMC-Na 71 mg/mL suspension

生物活性
靶点

  • Aurora A

    Aurora A, Ki:8 nM

  • Aurora B

    Aurora B, Ki:9 nM

  • VEGFR2

    VEGFR2, Ki:44 nM
描述 The aurora kinases, consisting of aurora A, B, and C, are a family of serine-threonine kinases that regulate centrosome maturation, bipolar spindle assembly, chromosome segregation, and cytokinesis. CYC-116 is a potent inhibitor for both aurora A and B with Ki values of 8.0 and 9.2nM, respectively. CYC-116 also inhibited CDK2/cyclin E, CDK4/cyclin D, CDK9/cyclin T, Flt-3, p70 S6, Src, Lck and VEGFR2 with Ki values of 0.39, 1.09, 0.48, 0.044, 0.54, 0.82, 2.80, and 0.044μM, respectively. iIn an MTT assay, CYC-116 inhibited A2780 and MiaPaCa-2 cell growth with IC50 values of 170 and 278nM, respectively. CYC-116 also exhibited anti-proliferative activity against MCF-7, Hela, Colo205, K562, NCI-H460, Saos-2, and Messa cell lines with IC50 values of 0.599, 0.590, 0.241, 1.375, 0.681, 0.110, and 0.090μM, respectively. In a murine P388/D1 leukemia model, oral administration of CYC-116 at 45 and 67mg/kg twice daily resulted in a significant increase in lifespan of 172% and 183%, respectively, as compared to the vehicle control group. In mice bearing subcutaneous NCI-H460 xenografts, oral dosing of CYC-116 at 75 and 100mg/kg/day caused tumor growth delays of 2.3 and 5.8 days, respectively.[3]
作用机制 CYC-116 is an inhibitor for aurora A and B that possesses anticancer activity.[3]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A2780 cells Cytotoxicity assay 96 h Cytotoxicity against human A2780 cells after 96 hrs by MTT assay 20462263
A549 cells 0.5-2 μM Function assay 7 h Cell cycle arrest in asynchronous human A549 cells assessed as accumulation of cyclin B1-negative tetraploid cells at G1 phase at 0.5 to 2 uM after 7 hrs by FACS analysis 20462263
A549 cells Function assay 7 h Inhibition of Aurora kinase in human A549 cells assessed as concentration required for half-maximal inhibition of histone H3 serine-10 phosphorylation after 7 hrs immunofluorescence microscopy 20462263
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.71mL

0.54mL

0.27mL

13.57mL

2.71mL

1.36mL

27.14mL

5.43mL

2.71mL
参考文献

[1]Kamei H, Jackson RC, et al. An integrated pharmacokinetic-pharmacodynamic model for an Aurora kinase inhibitor. J Pharmacokinet Pharmacodyn. 2010 Aug;37(4):407-34.

[2]Wang S, Midgley CA, et al. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem. 2010 Jun 10;53(11):4367-78.

[3]Wang S, Midgley CA, Scaërou F, et al. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem. 2010;53(11):4367-4378. doi:10.1021/jm901913s