Canertinib (CI-1033)
(Synonyms: 卡奈替尼; CI-1033; PD-183805) 目录号 : GC12910
Canertinib (CI-1033) (CI-1033;PD-183805) 是一种有效且不可逆的 EGFR 抑制剂；抑制细胞 EGFR 和 ErbB2 自磷酸化，IC50 为 7.4 和 9 nM。
Cas No.:267243-28-7
Sample solution is provided at 25 µL, 10mM.
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Canertinib (also known as CI-1033), a 3-chloro, 4-fluoro, 4-anilinoquinazoline, is an orally available, potent and irreversible Pan-erbB tyrosine kinase inhibitor that inhibits EGFR, HER2 and HER4 in vitro with the half maximal inhibition concentration IC50 of 0.8 nM, 19 nM and 7 nM respectively [1].
Canertinib irreversibly binds into the ATP pocket within the TK domain of all erbB family members, where the acrylamide side-chain at position C6 of canertinib is brought into close proximity with cysteines of erbB members, followed by the rapid formation of a covalent bond, which permanently inactivates the catalytically active erB1, erB2 and erB4 family members and effectively inhibits erbB3-dependent signaling [2].
References:
[1] Michelle Arkin, Mark M. Moasser. HER2 directed small molecule antagonists. Curr Opin Investig Drugs. Author manuscript; available in PMC 2011 February 1. Published in final edited form as: Curr Opin Investig Drugs. 2008 December; 9(12): 1264–1276.
[2] Calvo E, Tolcher AW, Hammond LA, Patnaik A, de Bono JS, Eiseman IA, Olson SC, Lenehan PF, McCreery H, Lorusso P, Rowinsky EK. Administration of CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a phase I pharmacokinetic and food effect study. Clin Cancer Res. 2004 Nov 1;10(21):7112-20.
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Kinase experiment: |
Enzyme assays for IC50 determinations are performed in 96-well filter plates. The total volume is 0.1 mL containing 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 µM adenosine triphosphate (ATP) containing 0.5 mCi of [32P]ATP, 20 mg of polyglutamic acid/tyrosine, 10 ng of EGFR tyrosine kinase, and appropriate dilutions of inhibitor (Canertinib). All components except the ATP are added to the well and the plate is incubated with shaking for 10 min at 25°C. The reaction is started by adding [32P]ATP, and the plate is incubated at 25°C for 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4°C for at least 15 min to allow the substrate to precipitate. The wells is then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a plate counter[1]. |
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Cell experiment: |
RaH3 and RaH5 cells are treated with increasing concentrations (0-10 μM) of Canertinib for 72 h. The cells are suspended in buffer and counted[2]. |
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Animal experiment: |
Mice: Canertinib treatment starts when the tumors show reliable growth. The mice are randomized into control and treatment groups. In the canertinib treated RaH3 group (n=4) and RaH5 group (n=7) each mouse receives i.p. injections of 1.2 mg canertinib (40 mg/kg/day) in 0.1 ml 0.15 M NaCl 5 days a week. The control RaH3 (n=3) and RaH5 (n=7) mice receive i.p. injections of vehicle only according to the same regimen. At the end of the treatment period, the mice are sacrificed by cervical dislocation where after the tumors are removed and weighed[2]. |
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References: [1]. Smaill JB, et al. Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions. J Med Chem. 2000 Apr 6;43(7):1380-97. |
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| Cas No. | 267243-28-7 | SDF | |
| 别名 | 卡奈替尼; CI-1033; PD-183805 | ||
| 化学名 | N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide | ||
| Canonical SMILES | C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4 | ||
| 分子式 | C24H25ClFN5O3 | 分子量 | 485.94 |
| 溶解度 | ≥ 12.15mg/mL in DMSO with gentle warming | 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 | 2.0579 mL | 10.2893 mL | 20.5787 mL |
| 5 mM | 0.4116 mL | 2.0579 mL | 4.1157 mL |
| 10 mM | 0.2058 mL | 1.0289 mL | 2.0579 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet