(E/Z)-Afatinib

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Chemical Structure| 439081-18-2 同义名 : (E/Z)-BIBW 2992
CAS号 : 439081-18-2
货号 : A369713
分子式 : C24H25ClFN5O3
纯度 : 98%
分子量 : 485.93
MDL号 : MFCD12407405
存储条件：

Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 EGFR (epidermal growth factor receptor) family consists of four members that belong to the ErbB lineage of proteins (ErbB1 - 4) with an external domain that binds activating ligands, such as EGF, and is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. Upon activation, EGFR phosphorylates both the receptor itself and a variety of “effector” protein. Afatinib is an irreversible inhibitor of pan-ErbB inhibitor with IC50 values of 0.4 nM, 0.5 nM, 10 nM, 14 nM and 1 nM for EGFR (L858R), EGFR (wt), EGFR (L858R/T790M), HER2[1] (measured by cell-free in vitro kinase assays) and ErbB4[2], respectively. Afatinib displays potent cellular effects on both EGFR and HER2 phosphorylation in cell lines with the in vitro kinase results, as well as anchorage-independent proliferation in NIH-3T3 cells ectopically expressing EGFR mutants. Afatinib inhibited survival of human NSCLC cell lines expressing HER2 776insV (NCI-H1781) or EGFR E746_A750del (HCC827), but showed no activity toward A549 cells, which expressed wild-type EGFR and HER2, but simultaneously harboring an oncogenic Kras G12S point mutation. Daily oral treatment with Afatinib at dose of 20 mg/kg for 25 days resulted in dramatic tumor regression and downregulation of EGFR and AKT phosphorylation in A431 cells xenografted models. Also the tumor regression by Afatinib can be observed in NCI-N87 cells and H1975 cells xenografted animals[1].
作用机制 Afatinib can form a covalent modification of the ATP-binding site in the kinase domains of EGFR (Cys 773) and HER2 (Cys 805)[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
22RV1 Growth Inhibition Assay IC50=34.1754 μM SANGER
23132-87 Growth Inhibition Assay IC50=0.31923 μM SANGER
5637 Growth Inhibition Assay IC50=1.0151 μM SANGER
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
NCT02145637 NSCLC Phase 1 Unknown July 2016 -
NCT01649284 - - - -
NCT03054038 Non-Small Cell Lung Carcinoma Phase 1 Recruiting March 2021 United States, California ... 展开 >> City of Hope National Medical Center Recruiting Duarte, California, United States, 91010 Contact: Thomas Fok       tfok@coh.org    Principal Investigator: Karen Reckamp, MD          Stanford Cancer Institute Recruiting Stanford, California, United States, 94035 Contact: Jordan Preiss    650-723-1002       Principal Investigator: Sukhmani Padda, MD          United States, Tennessee Vanderbilt-Ingram Cancer Center Recruiting Nashville, Tennessee, United States, 37232 收起 <<
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]Li D, Ambrogio L, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 7;27(34):4702-11.

[2]Ferrarotto R, Gold KA, et al. Afatinib in the treatment of head and neck squamous cell carcinoma. Expert Opin Investig Drugs. 2014 Jan;23(1):135-43.

[3]Hu X, Shi S, et al. Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo. Sci Rep. 2017 Jul 4;7(1):4559.

[4]Pharmacokinetics of afatinib