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Afatinib dimaleate

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Chemical Structure| 850140-73-7 同义名 : 马来酸阿法替尼 ;BIBW 2992MA2;Afatinib (maleate);BIBW 2992;BIBW2992 Dimaleate
CAS号 : 850140-73-7
货号 : A170920
分子式 : C32H33ClFN5O11
纯度 : 98%
分子量 : 718.083
MDL号 : MFCD25974239
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(48.74 mM)，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

H2O: 50 mg/mL(69.63 mM)，配合低频超声助溶
动物实验配方：

5% DMSO+30% PEG 300+water 28 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    EGFR (wt), IC50:0.5 nM

    EGFR (L858R/T790M), IC50:0.4 nM

  • HER2/ErbB2

    HER2, IC50:14 nM

  • HER2

    HER2, IC50:14 nM
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 Dimaleate is the dimaleate form of Afatinib. Afatinib is an irreversible inhibitor of pan-ErbB inhibitor with IC50 values of 0.4nM, 0.5nM, 10nM, 14nM and 1nM for EGFR (L858R), EGFR (wt), EGFR (L858R/T790M), HER2 (measured by cell-free in vitro kinase assays) and ErbB4, 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 20mg/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.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.96mL

1.39mL

0.70mL

13.93mL

2.79mL

1.39mL
参考文献

[1]Wang XK, He JH, et al. Afatinib enhances the efficacy of conventional chemotherapeutic agents by eradicating cancer stem-like cells. Cancer Res. 2014 Aug 15;74(16):4431-45.

[2]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.

[3]Afatinib Dimaleate