Canertinib

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Chemical Structure| 267243-28-7 同义名 : 卡纽替尼 ;CI-1033;PD-183805
CAS号 : 267243-28-7
货号 : A554853
分子式 : C24H25ClFN5O3
纯度 : 99%+
分子量 : 485.938
MDL号 : MFCD09837878
存储条件：

Pure form Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(8.23 mM)，配合水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 12 mg/mL(24.69 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

30% propylene glycol+5% Tween 80+65% water 10 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:1.5 nM

  • HER2/ErbB2

    ErbB2, IC50:9.0 nM

  • HER2

    ErbB2, IC50:9.0 nM
描述 Canertinib is a potent inhibitor of epidermal growth factor receptor (EGFR) with IC50 values of 7.4nM and 9nM for autophosphorylation of cellular EGFR and ErbB2, respectively[3]. Canertinib inhibited the proliferation of melanoma cell lines RaH3 and RaH5 at 2-10µM after 72 hours of treatment. Canertinib at 1µM and 10µM also inhibited melanoma cell cycle progression and induced apoptosis, respectively, after 24 hours of treatment. The phosphorylation of ErbB1, ErbB2, and ErbB3 receptor in melanoma cells was inhibited by canertinib at a concentration of 1µM. Canertinib at 40 mg/kg/day (i.p. injection) significantly inhibited tumor growth in mice bearing human malignant melanoma xenografts within 18 days of treatment[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A431 cells Function assay Inhibition of EGF-stimulated autophosphorylation of EGFR enzyme in A431 cells detected by immunoblotting, IC50=0.0074 μM 10753475
human A431 cells Proliferation assay 72 h Antiproliferative activity against human A431 cells overexpressing EGFR after 72 hrs by MTS assay, IC50=0.15 μM 22339342
human A431 cells 1 μM Function assay 1 h Irreversible inhibition of EGFR autophosphorylation in human A431 cells at 1 uM incubated for 1 hr followed by compound wash out measured 5 hrs post EGF addition by Western blotting analysis 24900594
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00174356 Carcinoma, Non-Small Cell Lung Phase 1 Completed - United States, Florida ... 展开 >> Pfizer Investigational Site Tampa, Florida, United States, 33612 United States, Illinois Pfizer Investigational Site Park Ridge, Illinois, United States, 60068 Pfizer Investigational Site Skokie, Illinois, United States, 60076 United States, Kentucky Pfizer Investigational Site Louisville, Kentucky, United States, 40202 Pfizer Investigational Site Louisville, Kentucky, United States, 40207 United States, Texas Pfizer Investigational Site Houston, Texas, United States, 77030 Canada, Ontario Pfizer Investigational Site Hamilton, Ontario, Canada, L8V 5C2 收起 <<
NCT00050830 Lung Neoplasms Phase 2 Completed - -
NCT00051051 Breast Neoplasms Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.06mL

0.41mL

0.21mL

10.29mL

2.06mL

1.03mL

20.58mL

4.12mL

2.06mL
参考文献

[1]Nelson JM, Fry DW. Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition. J Biol Chem. 2001 May 4;276(18):14842-7.

[2]Smaill JB, Rewcastle GW, 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.

[3]Smaill JB, Rewcastle GW, Loo JA, 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):1380-1397

[4]Djerf Severinsson EA, Trinks C, Gréen H, et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. Biochem Biophys Res Commun. 2011;414(3):563-568