Gefitinib-ZD1839-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGefitinibCat. No.: HY-50895CAS No.: 184475-35-2Synonyms: ZD1839分式: CHClFNO分量: 446.9作靶点: EGFR; Autophagy作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、 1 month溶解性数据体外实验 DMSO : 50 mg/mL (111.88 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2376 mL 11.1882 mL 22.3764 mL5 mM 0.4475 mL 2.2376 mL 4.4753 mL10 mM 0.2238 mL 1.1188 mL 2.2376 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择

3、适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.59 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.59 mM); Clear solution1/3 Maste

4、r of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Gefitinib种有效的表长因受体 (EGFR) 抑制剂，在 NR6wtEGFR 细胞中 IC50 值为 2-37 nM。IC50 & Target EGFR体外研究 Gefitinib (0.01-0.1 mM) results in increased phosphotyrosine load of the receptor, increased signalling toERK and stimulation of proliferation and ancho

5、rage-independent growth, presumably by inducing EGFRvIIIdimerisation in long-term exposure of EGFRvIII-expressing cells. On the other hand, gefitinib (1-2 mM)significantly decreases EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation and anchorage-independent growth 1. Gefitinib (ZD1839)

6、inhibits the monolayer growth of these EGF-driven untransformedcells with IC50 of 20 nM 2. Gefitinib leads to an inhibition of CALU-3 and GLC82 cell proliferation, with anIC50 of 2 M 3.体内研究 Gefitinib (150 mg/kg, p.o.) in conbination with Metformin induces a significant reduction in tumor growth innu

7、de mice bearing H1299 or CALU-3 GEF-R cells that are grown subcutaneously as tumor xenografts 3. Inirradiated rats, Gefitinib treatment augmentes lung inflammation, including inflammatory cell infiltration andpro-inflammatory cytokine expression, while Gefitinib treatment attenuates fibrotic lung re

8、modeling due to theinhibition of lung fibroblast proliferation 4.PROTOCOLCell Assay 3 Cancer cells are seeded in 96-well plates and are treated with different doses of Gefitinib (0.01-20 M),Metformin or both for 72 hours. Cell proliferation is measured with the MTT assay. The IC50 values aredetermin

9、ed by interpolation from the dose-response curves. Results represent the median of 3 separateexperiments each conducted in quadruplicate. The results of the combined treatment are analyzed accordingto the method of Chou and Talalay by using the CalcuSyn software program 3.MCE has not independently c

10、onfirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 34 Four- to 6-week old female balb/c athymic (nu+/nu+) mice are acclimatized for 1 week before being injectedwith cancer cells and injected subcutaneously with 107 H1299 and CALU-3 GEF-R cells that has be

11、enresuspended in 200 L of Matrigel. When established tumors of approximately 75 mm3 in diameter aredetected, mice are left untreated or treated with oral administrations of metformin (200 mg/mL metformindiluted in drinking water and present throughout the experiment), gefitinib (150 mg/kg daily oral

12、ly by gavage),or both for the indicated time periods. Each treatment group consists of 10 mice. Tumor volume is measuredusing the formula /6larger diameter(smaller diameter)2.Rats 4The rats are randomly assigned to 1 of 4 experimental groups: 1) the unirradiated rats treated with oraladministration

13、of vehicle (0.1% Tween 80) once daily; 2) the unirradiated rats treated with oral administrationof gefitinib (50 mg/kg/day) once daily; 3) the irradiated rats treated with oral administration of vehicle oncedaily; 4) the irradiated rats treated with oral administration of gefitinib once daily. Each

14、experimental group2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEcomprised 5-6 rats and all treatments are delivered for 14 days.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cancer Cell. 2018 Jun 11;33(6):1061-1077.e6. Sci Transl Med. 2

15、018 Jul 18;10(450). pii: eaaq1093. Nat Commun. 2019 Apr 18;10(1):1812 Theranostics. 2018 Jul 30;8(15):4262-4278. Cell Rep. 2019 Jul 9;28(2):512-525.e6.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Pedersen MW, et al. Differential response to gefitinib of cells expressing norm

16、al EGFR and the mutant EGFRvIII. Br J Cancer. 2005 Oct17;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. Synergisti

17、c effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, inLKB1 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, b

18、ut attenuates lung fibrosisin 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 pharmacokineticstudy in rats. J Sep Sci. 2017 Jul 27.6. Dhar D, et al. Liver Cancer Initiation Requires p53 Inhibition by CD44-En