|3-((4-(6-溴-2-(4-(4-甲基哌嗪-1-基)苯基)-3H-咪唑并[4,5-b]吡啶-7-基)哌嗪-1-基)甲基)-5-甲基异恶唑|CsnPharm

CAS No.: 1095382-05-0

CCT 137690 Catalog No. CSN17149

Synonyms: CCT137690

CCT137690 is a potent inhibitor of Aurora kinases (IC50 values are 0.015, 0.019 and 0.025 μM at Aurora A, Aurora C and Aurora B respectively).

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

描述Aurora kinases are a family of 3 highly homologous serine/threonine kinases, and include 3 major members, AURKA, AURKB, and AURKC, that play a well-known role in the regulation of cell cycle and division. CCT137690, a pan-Aurora inhibitor, inhibits the proliferation of cancer cell lines of different origins including colorectal, ovarian, neuroblastoma and leukemia. CCT137690 is a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinases with low nanomolar IC₅₀ values. The IC₅₀ values are 15 nM, 25 nM, and 19 nM for aurora A, B and C, respectively. CCT137690 efficiently inhibits histone H3 and transforming acidic coiled-coil 3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumor cells to CCT137690 causes multipolar spindle formation, chromosome misalignment, polyploidy, and apoptosis. The PDAC cell lines (PANC1, PANC2.03, CFPAC1, MiaPaCa2, BxPc3, and PANC02) and normal HPDEs cell line were used to identify CCT137690 with anticancer activity against PDAC ( pancreatic ductal adenocarcinoma cancer). Cells were treated with CCT137690 range from 0 - 40 μM for 24 hours, and the PDAC cells viability were significantly decreased by a dose depend manner. In contrast, normal HPDEs were resistant to CCT137690 treatment. Colony formation assays confirmed that the reproductive integrity of the PDAC cells after CCT137690 treatment was significantly reduced. Altogether, these results suggest that CCT137690 has anticancer activity in human PDAC cells. Human PANC1 cells implanted mice were administered CCT137690 orally at 80 mg/kg consecutively for 40 days. Compared with the vehicle control group, administration of CCT137690 effectively reduced tumor growth. Western blot analysis of indicated protein expressions in isolated tumor at day 34 showed that CCT137690 reduced the local phosphorylation of AURKA and GSK3β. These data demonstrated that CCT137690 significantly suppressed PDAC growth in vitro and in vivo through induction of necroptosis^[3].
作用机制CCT137690 binds with Aurora-A enzyme, and the pyridine N and imidazole NH are interacting with Ala213 in the hinge region of the kinase. It occupies the ATP-binding site with the activation loop in a DFG-in conformation. The pyridine N is hydrogen bonded to backbone NH of Ala213 and the imidazole NH to the carbonyl of Ala213^[4].
动物研究
剂量
Mice: 40 mg/kg, 80 mg/kg^[3] (p.o., twice every other day for 2 weeks), 100 mg/kg^[1] (p.o., twice daily for 10 days)

给药途径
p.o.
参考文献

动物研究
剂量	Mice: 40 mg/kg, 80 mg/kg^[3] (p.o., twice every other day for 2 weeks), 100 mg/kg^[1] (p.o., twice daily for 10 days)
给药途径	p.o.

[1] Faisal A, Vaughan L, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115-23.
[2] Bavetsias V, Large JM, et al. Imidazo[4,5-b] pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28.
[3] Xie Y, Zhu S, Zhong M, Yang M, Sun X, Liu J, Kroemer G, Lotze M, Zeh HJ 3rd, Kang R, Tang D. Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma. Gastroenterology. 2017 Nov;153(5):1429-1443.e5.
[4] Bavetsias V, Large JM, Sun C, Bouloc N, Kosmopoulou M, Matteucci M, Wilsher NE, Martins V, Reynisson J, Atrash B, Faisal A, Urban F, Valenti M, de Haven Brandon A, Box G, Raynaud FI, Workman P, Eccles SA, Bayliss R, Blagg J, Linardopoulos S, McDonald E. Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.8133 mL
- 9.0665 mL
- 18.1330 mL
- 5 mM
- 0.3627 mL
- 1.8133 mL
- 3.6266 mL
- 10 mM
- 0.1813 mL
- 0.9066 mL
- 1.8133 mL

技术信息

CAS号

1095382-05-0

储存条件

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

液体: -20°C:3-6 月 -80°C:12月

分子式

C26H31BrN8O

运输

蓝冰

分子量

551.48

别名

CCT137690

溶解度

DMSO	4.0 mg/mL (7.3 mM)
Water	Insoluble
Ethanol	Insoluble

动物实验配方

1% DMSO+30% polyethylene glycol+1% Tween 80+water

30 mg/mL

suspension

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

CCT 137690 Catalog No. CSN17149

靶点选择性

请登录您的专属账户

确认信息