Gefitinib

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Chemical Structure| 184475-35-2 同义名 : 吉非替尼 (ZD1839) ;ZD1839
CAS号 : 184475-35-2
货号 : A109874
分子式 : C22H24ClFN4O3
纯度 : 98%
分子量 : 446.9
MDL号 : MFCD04307832
存储条件：

Pure form Keep in dark place,Sealed in dry,Room Temperature

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

DMSO: 105 mg/mL(234.95 mM)，配合低频超声助溶，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
动物实验配方：

1% CMC Na+water 30 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    Tyr992 (NR6wtEGFR cells), IC50:37 nM

    Tyr1173 (NR6W cells), IC50:57 nM

  • EGFR/ErbB1

    EGFR, IC50:15.5 nM

  • mutant EGFR

    EGFR (858R/T790M), IC50:823.3 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. Gefitinib is an effective EGFR inhibitor with IC50 values of 37 nM, 37 nM, 26 nM and 57 nM for Tyr1173, Tyr992, Tyr1173 and Tyr992 EGFR sites (measured by EGFR tyrosine phosphorylations in cells), respectively in NR6 wt EGFR and NR6W cells. Gefitinib can sufficiently suppress all tyrosine phosphorylation sites, with less sensitivity to Tyr1173 and Tyr992 sites, on EGFR in both the high and low-EGFR-expressing cell lines, as well as EGFR-mediated proliferation. However, EGFR-mediated anchorage-independent growth was not sufficient to inhibit these features in cells expressing EGFRvIII, with approximately four times as resistant to gefitinib as EGFR. Long-term exposure of EGFRvIII-expressing cells to low concentrations of gefitinib (0.01 - 0.1 μM) resulted in increased phosphotyrosine load of the receptor, increased signaling to ERK and stimulation of proliferation and anchorage-independent growth while higher concentrations of gefitinib (1 - 2 μM) completely showed the opposite effect, presumably by inducing EGFRvIII dimerization[1]. Gefitinib (40 mg/kg body weight/day) showed significant inhibition of tumor load when treated with weekly or weekly intermittent dosing regimens in lung adenocarcinoma model whereas a daily dosing regimen did not decrease the tumor load significantly[2].
作用机制 Gefitinib is an ATP-competitive inhibitor of EGFR[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
16HBE Growth Inhibition Assay 72 h Antiproliferative activity against human 16HBE cells expressing wild type EGFR with IC50 of 1.601 μM 23792318
16HBE 100 μM Function Assay 150 min Induction of nitric oxide production in human 16HBE cells expressing wild type EGFR 23792318
16HBE14o- 10 μM Cytotoxic Assay 72 h Cytotoxicity against human 16HBE14o- cells harboring wild type EGFR assessed as growth inhibition with IC50 of 12.71 μM 23668441
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
NCT00206414 BREAST CANCER Phase 2 Terminated(Difficulty accruing... 展开 >> subjects the study accrual was closed) 收起 << - United States, Texas ... 展开 >> Baylor Breast Center Houston, Texas, United States, 77030 收起 <<
NCT00820417 Colorectal Cancer ... 展开 >> Head and Neck Cancer Non Small Cell Lung Cancer (NSCLC) 收起 << Phase 1 Completed - Belgium ... 展开 >> UZ Gasthuisberg Leuven, Belgium, 3000 Spain Hospital Universitari Vall d'Hebron Barcelona, Spain, 08035 收起 <<
NCT00025207 Advanced Malignant Mesotheliom... 展开 >>a Epithelial Mesothelioma Recurrent Malignant Mesothelioma Sarcomatous Mesothelioma 收起 << Phase 2 Completed - United States, Illinois ... 展开 >> Cancer and Leukemia Group B Chicago, Illinois, United States, 60606 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.24mL

0.45mL

0.22mL

11.19mL

2.24mL

1.12mL

22.38mL

4.48mL

2.24mL
参考文献

[1]Pedersen MW, Pedersen N, et al. Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br J Cancer. 2005 Oct 17;93(8):915-23.

[2]Zhang Q, Li R, et al. Effect of weekly or daily dosing regimen of Gefitinib in mouse models of lung cancer. Oncotarget. 2017 Aug 2;8(42):72447-72456.

[3]Gokhale AG, Rajagopal P, et al. Cockroach in right main bronchus--an unusual foreign body. Indian J Chest Dis Allied Sci. 1992 Apr-Jun;34(2):103-5.

[4]Kishino D, Kiura K, et al. Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mice. Lung Cancer. 2009 Sep;65(3):284-9.

[5]Mikumo H, Yanagihara T, et al. Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice. Biochem Biophys Res Commun. 2017 Apr 22;486(1):205-209.

[6]Pharmacokinetics of gefitinib