Canertinib dihydrochloride
(Synonyms: 卡纽替尼二盐酸盐,PD-183805; CI-1033;Canertinib HCl;PD183805; CI103;PD 183805; CI 103) 目录号 : GC12087
A pan-ErbB tyrosine kinase inhibitor
Cas No.:289499-45-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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]. |
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]. |
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]. |
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. | |
Canertinib dihydrochloride is a selective inhibitor of Pan-erbB tyrosine kinase with IC50 value of 3.5 nM [1].
ErbB receptor family is a member of the receptor tyrosine kinase superfamily and plays an important role in the normal breast development. It has been shown that ErbB overexpression involves in the pathogenesis and progression of breast cancer and is a negative prognostic indicator for breast cancer [2].
Canertinib dihydrochloride is a potent ErbB inhibitor and has a different selectivity with the reported ErbB inhibitor erlotinib. When tested with BT474 cells overexpressing ErbB2-receptor, treatment with Canertinib dihydrochloride induced cell apoptosis with 47% fraction by inhibiting Akt and MAPK activity [3]. In a panel of neuroblastoma cell lines, treated with Canertinib dihydrochloride resulted in a significant reduction in cell yield with IC50 value ranging from 0.94 μM to 2.45 μM and induced cell apoptosis from 3% to 56% tested with SK-N-SH cells [2].
In 12 week old NOD-SCID-IL2R gamma knockout mouse model with SK-N-SH cells subcutaneous xenograft, administration of Canertinib dihydrochloride for 18 days resulted in a marked reduction in tumor growth and final tumor weight [2].
References:
[1].Smaill, J.B., 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. 43(7): p. 1380-97.
[2].Richards, K.N., et al., Signaling of ERBB receptor tyrosine kinases promotes neuroblastoma growth in vitro and in vivo. Cancer, 2010. 116(13): p. 3233-43.
[3].Nelson, J.M. and D.W. Fry, Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition. J Biol Chem, 2001. 276(18): p. 14842-7.
| Cas No. | 289499-45-2 | SDF | |
| 别名 | 卡纽替尼二盐酸盐,PD-183805; CI-1033;Canertinib HCl;PD183805; CI103;PD 183805; CI 103 | ||
| 化学名 | N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide;dihydrochloride | ||
| Canonical SMILES | C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4.Cl.Cl | ||
| 分子式 | C24H27Cl3FN5O3 | 分子量 | 558.87 |
| 溶解度 | ≥ 55.9 mg/mL in DMSO with gentle warming, ≥ 8.96 mg/mL in EtOH with ultrasonic and warming, ≥ 21.8 mg/mL in Water with ultrasonic and 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 | 1.7893 mL | 8.9466 mL | 17.8932 mL |
| 5 mM | 0.3579 mL | 1.7893 mL | 3.5786 mL |
| 10 mM | 0.1789 mL | 0.8947 mL | 1.7893 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。