您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > Canertinib dihydrochloride
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Canertinib dihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Canertinib dihydrochloride图片
包装与价格:
包装价格(元)
50mg电议
10mg电议
100mg电议
500mg电议

产品介绍
Canertinib dihydrochloride (CI-1033 dihydrochloride) 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。

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℃. The reaction is started by adding [32P]ATP, and the plate is incubated at 25℃ for 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4℃ 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].

产品描述

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.