| CAS |
184475-35-2 |
| Chinese Name |
吉非替尼 |
| English Name |
Gefitinib |
| Synonyms |
吉非替尼;SR-47436;BMS-186295;易瑞沙; |
| Molecular Formula |
C22H24ClFN4O3 |
| Molecular Weight |
446.9 |
| Solubility |
Soluble in DMSO |
| Purity |
HPLC≥98% |
| Appearance |
White to off-white Solid |
| Storage |
Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 643-034-7 |
| MDL |
MFCD04307832 |
| SMILES |
ClC1=C(C=CC(NC2=NC=NC3=C2C=C(C(OC)=C3)OCCCN4CCOCC4)=C1)F |
| InChIKey |
XGALLCVXEZPNRQ-UHFFFAOYSA-N |
| InChI |
InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27) |
| PubChem CID |
123631 |
| Target Point |
EGFR |
| Passage |
Angiogenesis;Protein Tyrosine Kinase/RTK; JAK/STAT Signaling |
| Background |
It is an effective and selective EGFR tyrosine kinase inhibitor and can also induce autophagy. It has anti-tumor activity. |
| Biological Activity |
Gefitinib 是一种有效的表皮生长因子受体 (EGFR) 抑制剂，在 NR6wtEGFR 细胞中 IC50 值为 2-37 nM。[1-6] |
| In Vitro |
吉非替尼(0.01-0.1mM)导致受体的磷酸酪氨酸负荷增加，ERK信号传导增加和刺激增殖和锚定非依赖性生长，可能是通过在EGFRvIII表达细胞的长期暴露中诱导EGFRvIII二聚化。另一方面，吉非替尼(1-2 mM)显著降低EGFRvIII磷酸酪氨酸负荷，EGFRvIII介导的增殖和不依赖贴壁的生长[1]。吉非替尼(ZD1839)抑制这些EGF驱动的未转化细胞的单层生长，IC50为20 nM [2]。吉非替尼可抑制CALU-3和GLC82细胞增殖，IC50为2μM[3]。 |
| In Vivo |
与二甲双胍混合的吉非替尼(150mg/kg，口服)诱导携带H1299或CALU-3 GEF-R细胞的裸鼠中肿瘤生长的显著降低，所述细胞作为肿瘤异种移植物皮下生长[3]。在受照射的大鼠中，吉非替尼治疗可增强肺部炎症，包括炎症细胞浸润和促炎细胞因子表达，而吉非替尼治疗可减轻由于肺成纤维细胞增殖抑制引起的纤维化肺重塑[4]。 |
| Cell Experiment |
将癌细胞接种在96孔板中，并用不同剂量的吉非替尼(0.01-20μM)，二甲双胍或两者处理72小时。用MTT测定法测量细胞增殖。通过剂量 - 反应曲线的内插确定IC 50值。结果表示3个单独实验的中值，每个实验一式四份进行。通过使用CalcuSyn软件程序[3]，根据Chou和Talalay的方法分析组合处理的结果。 |
| Animal Experiment |
小鼠[3] 4至6周龄雌性balb/c无胸腺(nu +/nu +)小鼠在注射癌细胞前适应环境1周，皮下注射107 H1299和CALU-3 GEF-R细胞重悬于200μLMatrigel中。当检测到直径约75mm3的确定肿瘤时，小鼠不进行治疗或口服二甲双胍(200mg/mL二甲双胍稀释于饮用水中并在整个实验中存在)，吉非替尼(150mg/kg，每天口服灌胃))或指定时间段内的两者。每个治疗组由10只小鼠组成。使用公式π/ 6×较大直径×(较小直径)2测量肿瘤体积。大鼠[4]将大鼠随机分配到4个实验组中的1个：1)每天一次口服给予载体(0.1％吐温80)治疗的未照射大鼠; 2)每日一次口服吉非替尼(50mg/kg /天)治疗的未照射大鼠; 3)每天一次口服给药治疗的受照射大鼠; 4)每天一次口服吉非替尼治疗的受照射大鼠。每个实验组包含5-6只大鼠，并且所有处理都被递送14天。 |
| Data Literature Source |
[1]. Pedersen MW，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]. Moasser MM，et al. The tyrosine kinase inhibitor ZD1839 ('Iressa') inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 2001 Oct 1;61(19):7184-8.
[3]. Morgillo F，et al. Synergistic effects of metformin treatment in combination with gefitinib，a selective EGFR tyrosine kinase inhibitor，in LKB1 wild-type NSCLC cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3508-19.
[4]. Miyake K，et al. Epidermal growth factor receptor-tyrosine kinase inhibitor (gefitinib) augments pneumonitis，but attenuates lung fibrosis in response to radiation injury in rats. J Med Invest. 2012;59(1-2):174-85.
[5]. Noh CK，et al. Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC-MS/MS for application to a pharmacokinetic study in rats. J Sep Sci. 2017 Jul 27.
[6]. Dhar D，et al. Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell. 2018 Jun 11;33(6):1061-1077.e6. |
| Unit |
Bottle |
| Specification |
10mg 10mM*1mL in DMSO 50mg |
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