AZD6244(Selumetinib)
(Synonyms: 司美替尼; AZD6244; ARRY-142886) 目录号 : GC17030
A highly selective inhibitor of MEK1/2
Cas No.:606143-52-6
Sample solution is provided at 25 µL, 10mM.
AZD6244 is a highly potent and selective inhibitor of MEK1/2 with IC50 value of 14.1nM against MEK1 [1].
AZD6244 is a second generation MEK1/2 inhibitor. In the radioactive assay, AZD6244 shows potent inhibition against the purified MEK1without the competition with ATP. Besides, it is a selective inhibitor since it has no obvious inhibition against other tyrosine kinases including MKK6, EGFR, ErbB2 and B-Raf et al. In the cellular assay, AZD6244 inhibits the phosphorylation of ERK1/2 which are the direct substrates of MEK1/2. The IC50 value is 10.3nM. It also inhibits the EGF-induced phosphorylation of ERK1/2 but not ERK5 in A431 cells. Since MEK is important in cell proliferation, the block of MEK1/2 caused by AZD6244 leads to a growth inhibition in the cell lines containing activating B-Raf and Ras mutations with IC50 values ranging from 59 to 473nM. Furthermore, the administration of AZD6244 can significantly inhibit tumor growth both in the HT-29 xenograft model and the BxPC3 pancreatic tumor xenograft model [1].
References:
[1] Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, Parry J, Smith D, Brandhuber BJ, Gross S, Marlow A, Hurley B, Lyssikatos J, Lee PA, Winkler JD, Koch K, Wallace E. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
| Cell experiment: [1] | |
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Cell lines |
1205Lu cells (BRAFV600E) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
3 μM, 24 hours |
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Applications |
Inhibition of cell growth by AZD6244 is caused by reversible G1 -phase cell cycle arrest. Adherent 1205Lu cells were treated with DMSO or 3 μM AZD6244 for 24 h or for 24 h and a further 24 h after removal of the drugs. Cells treated with AZD6244 were found to enter into the G1 -phase cell cycle arrest, but to reenter S phase after removal of the drug. |
| Animal experiment: [2] | |
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Animal models |
Nude mice implanted with HT-29 human colon carcinoma |
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Dosage form |
Oral administration, 10, 25, 50, or 100 mg/kg, twice a day for 21 days |
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Applications |
AZD6244 is effective in inhibiting tumor growth at all doses tested. The time to the tumor growth end point was 36 days for the two highest dose groups compared with 18 days for the vehicle control group. Tumor growth after 11 days of dosing was inhibited by 55% at the low dose of 10 mg/kg and by 70% at the high dose of 100 mg/kg. Recovery of tumor growth was observed after cessation of AZD6244 administration. Tumor regrowth was significantly delayed in the 100 mg/kg dose group. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Haass N K, Sproesser K, Nguyen T K, et al. The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clinical Cancer Research, 2008, 14(1): 230-239. [2] Yeh T C, Marsh V, Bernat B A, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clinical Cancer Research, 2007, 13(5): 1576-1583. | |
| Cas No. | 606143-52-6 | SDF | |
| 别名 | 司美替尼; AZD6244; ARRY-142886 | ||
| 化学名 | 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide | ||
| Canonical SMILES | CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO | ||
| 分子式 | C17H15BrClFN4O3 | 分子量 | 457.69 |
| 溶解度 | ≥ 22.9mg/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 | 2.1849 mL | 10.9244 mL | 21.8488 mL |
| 5 mM | 0.437 mL | 2.1849 mL | 4.3698 mL |
| 10 mM | 0.2185 mL | 1.0924 mL | 2.1849 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