CCT137690
(Synonyms: 甲磺酸阿贝西尼) 目录号 : GC14566
An inhibitor of Aurora kinases and FLT3
Cas No.:1095382-05-0
Sample solution is provided at 25 µL, 10mM.
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CCT137690 is an orally bioavailable inhibitor of aurora kinases with IC50 values in a range from 15 to 25 nM [1].
Aurora kinase is a family of serine/threonine kinases including Aurora-A, B and C. They play important roles in the regulation of mitosis and take participate in the causation and progression of various tumors including ovarian, breast, glioma and colon. Therefore aurora kinases have been regarded as anti-cancer targets in cancer chemotherapeutics.CCT137690 is a selective small-molecular inhibitor of aurora kinases and showed anti-tumor activities both in vitro and in vivo. Besides that, CCT137690 exerted good stability in mouse liver microsomes [1].
When tested toward a panel of 94 kinases, CCT137690inhibited 80% activities of VEG-FR, Aurora-A, and FGF-R1 at concentration of 1 μM. It suppressed the phosphorylation of histone H3 caused by Aurora-B. The IC50 values of CCT137690 against Aurora-B and C were 25 and 19 nM, respectively. CCT137690 showed potent anti-proliferation effects on various kinds of tumors such as A2780 ovarian tumor cell (IC50 value of 140 nM), SW620 (IC50 value of 300 nM) and SW48 colon carcinoma (IC50 value of 157 nM). It caused cell cycle perturbations. In addition, CCT137690 was found to have synergistic effects with radiotherapy. It increased the sensitivity of SW620 cells to radiation. The combination treatment resulted in much more cell death through apoptosis [1 and 2].
In mice model bearing SW620 xenografts, administration of CCT137690slowed the growth of tumors without observed toxicity. The ratio of treat/control group based on tumor weight was 37% at the dose of 75 mg/kg. Besides that, CCT137690 was found to significantly reduced neuroblastoma tumor mass in MYCN transgenic mice, which meant CCT137690 could benefit patients with MYCN-amplified neuroblastoma [1 and 3].
References:
[1] Bavetsias V, Large J M, Sun C, 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. Journal of medicinal chemistry, 2010, 53(14): 5213-5228.
[2] Wu X, Liu W, Cao Q, et al. Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy. J ExpClin Cancer Res, 2014, 33(1): 13.
[3] Faisal A, Vaughan L, Bavetsias V, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Molecular cancer therapeutics, 2011, 10(11): 2115-2123.
Cell experiment: | Cells are plated in 96-well plates at 3,000 cells per well and are treated with a range of 0 to 25 mol/L of CCT137690 for 72 h. Cell proliferation assays are performed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)[2]. |
Animal experiment: | Mice: Animals are randomized into two groups, group 1: treatment with 100 mg/kg CCT137690 n=4 or group 2: vehicle control n=4. Treatment is administered via oral gavage twice daily. Tumour volumes are measured at day 0, 3 (48 hours after treatment started), 7 and 10 using 1H MRI[2]. |
References: [1]. Bavetsias V, 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. | |
| Cas No. | 1095382-05-0 | SDF | |
| 别名 | 甲磺酸阿贝西尼 | ||
| 化学名 | 3-[[4-[6-bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-5-methyl-1,2-oxazole | ||
| Canonical SMILES | CC1=CC(=NO1)CN2CCN(CC2)C3=C4C(=NC=C3Br)N=C(N4)C5=CC=C(C=C5)N6CCN(CC6)C | ||
| 分子式 | C26H31BrN8O | 分子量 | 551.48 |
| 溶解度 | ≥ 6.9 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8133 mL | 9.0665 mL | 18.133 mL |
| 5 mM | 0.3627 mL | 1.8133 mL | 3.6266 mL |
| 10 mM | 0.1813 mL | 0.9067 mL | 1.8133 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet