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Gefitinib(Iressa)

产品号 S1025 公司名称 Selleck Chemicals
CAS号 184475-35-2 公司网站 http://www.selleckchem.com
分子式 C22H24ClFN4O3 电 话 (877) 796-6397
分子量 446.9023632 传 真 (832) 582-8590
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保 存 -20°C Chembase数据库ID: 202

产品价格信息

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产品别名

标题
Gefitinib(Iressa)
IUPAC标准名
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine
IUPAC传统名
gefitinib
别名
Iressa
ZD-1839

产品登记号

CAS号 184475-35-2

产品性质

作用靶点 EGFR
成盐信息 Free Base
溶解度 DMSO
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Glioblastoma, Bladder cancer
Biological Activity
Description Gefitinib (Iressa, ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively.
Targets Tyr1173 (NR6wtEGFR cells) Tyr992 (NR6wtEGFR cells) Tyr1173 (NR6W cells) Tyr992 (NR6W cells)
IC50 37 nM 37nM 26 nM 57 nM [1]
In Vitro Gefitinib effectively inhibits all tyrosine phosphorylation sites on EGFR in both the high and low-EGFR-expressing cell lines including NR6, NR6M and NR6W cell lines. The phosphorylation sites Tyr1173 and Tyr992 are less sensitive requiring higher concentrations of Gefitinib for inhibition. Gefitinib effectively blocks the phosphorylation of PLC-γ, with IC50 of 27nM, in NR6W cells. The NR6wtEGFR and NR6M cell lines has low levels of PLC-γ phosphorylation but the level in the NR6M cell line is more resistant to inhibition by Gefitinib with IC50 of 43 nM and 369 nM, respectively. Gefitinib inhibits Akt phosphorylations, with IC50 of 220 and 263nM, in the low-EGFR- and -EGFRvIII-expressing cell lines, respectively. Gefitinib in the dose range from 0.1 to 0.5μM significantly facilitates, rather than abrogates, colony formation of NR6M cells. However, at a concentration of 2 μM Gefitinib completely blocks NR6M colony formation. Gefitinib rapidly and in a dose-dependent manner inhibits EGFR and ERK phosphorylation up to 72 hours after EGF stimulation in both the high- and low-EGFR-expressing cell lines. [1] Gefitinib is the monolayer growth of these EGF-driven untransformed MCF10A cells with an IC50 of 20 nM. [2] Gefitinib blocks EGF signalling in MDA-MB-231 cells. Gefitinib severely inhibits this increase in cell number in a dose-dependent manner. [3]
In Vivo Gefitinib inhibits tumour growth of SKOV3 or MDA-MB-231 tumors in athymic nude mice. Gefitinib is effective against both types of tumour. Growth of MDA-MB-231 tumors over the 14-day treatment period is inhibited by approximately 71% and that of SKOV3 tumors by approximately 32%. [3] Gefitinib treatment of nude mice bearing established human GEO colon cancer xenografts reveals a reversible dose-dependent inhibition of tumor growth because GEO tumors resumes the growth rate of controls at the end of the treatment. [4]
Clinical Trials Gefitinib has entered in a phase II clinical trial in the treatment of non small cell lung cancer.
Features Gefitinib is a potent EGFR tyrosine kinase inhibitor.
Combination Therapy
Description Coadministration of Gefitinib, as with anti-EGFR, will enhance the efficacy of cytotoxic agents against human vulvar (A431), lung (A549 and SK-LC-16 NSCL and LX-1), and prostate (PC-3 and TSU-PR1) tumors. Although Paclitaxel or Docetaxel, as single agents markedly inhibits the growth of A431, LX-1, SK-LC-16, TSU-PR1, and PC-3, when combined with Gefitinib, partial or complete regression is usually seen. Against A549, the growth inhibition of Doxorubicin is increased 10-fold (>99%) with Gefitinib. [5]
Protocol
Cell Assay [1]
Cell Lines NR6, NR6M and NR6W cells
Concentrations 0-2 μM
Incubation Time 72 hours
Methods Exponentially growing cells including NR6, NR6M, NR6M and NR6W cells are seeded in sextuple in 96-well plates at a concentration of 2000 cells/well, allowed to adhere and subsequently washed in PBS and incubated overnight in medium containing 0.5% FCS. Cells are then treated with varying concentrations (0-2 μM) of Gefitinib or the solute control DMSO and EGF. The optimal EGF concentration for inducing proliferation of NR6wtEGFR and NR6W cells has previously been determined and hence NR6wtEGFR and NR6W cells are supplemented with 10 nM and 0.1 nM EGF, respectively. EGF is not added to NR6 and NR6M cells. After 72 hours the amount of cells are measured by performing a MTT proliferation assay.
Animal Study [3]
Animal Models Athymic nude mice bearing SKOV3 or MDA-MB-231 tumours
Formulation 0.2% DMSO
Doses 75 mg/kg
Administration Gavage
References
[1] Pedersen MW, et al. Br J Cancer. 2005, 93(8), 915-923.
[2] Moasser MM, et al. Cancer Res. 2001, 61(19), 7184-7188.
[3] Anderson NG, et al. Int J Cancer. 2001, 94(6), 774-782.
[4] Ciardiello F, et al. Clin Cancer Res. 2000, 6(5), 2053-2063.
[5] Sirotnak FM, et al. Clin Cancer Res. 2000, 6(12), 4885-4892.