Gefitinib (ZD1839)

Catalog No.S1025

Gefitinib (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.

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Gefitinib (ZD1839) Chemical Structure

Gefitinib (ZD1839) Chemical Structure
Molecular Weight: 446.90

Validation & Quality Control

Cited by 90 publications:

11 customer reviews :

Quality Control & MSDS

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Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Gefitinib (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 (NR6W cells) [1] Tyr1173 (NR6wtEGFR cells) [1] Tyr992 (NR6wtEGFR cells) [1] Tyr992 (NR6W cells) [1]
IC50 26 nM 37 nM 37 nM 57 nM
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] The combination of Gefitinib (0.2 μM and 0.5 μM) with irradiation lead to a significant growth inhibition in LoVo cells, compared with radiation alone.. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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HCC1395NV\5PXprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXv4eYxZUUN3ME20PE44PDN{IN88US=>MlnmV2FPT0WU

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In vivo Gefitinib (100 mg/kg) improves the anti-tumor effect of radiotherapy in LoVo tumor xenografts. [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]
Features A potent EGFR tyrosine kinase inhibitor.

Protocol(Only for Reference)

Cell Assay: [1]

Cell lines NR6, NR6M and NR6W cells
Concentrations 0-2 μM
Incubation Time 72 hours
Method 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 Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.
Formulation 0.5% polysorbate
Dosages 100 mg/kg
Administration Once daily by oral administration (0.1 mL/10 g body weight) for 14 days

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

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.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02836847 Recruiting Cholangiocarcinoma of the Extrahepatic Bile Duct|Gallbladder Cancer Shanghai Jiao Tong University School of Medicine|Xinhua H  ...more Shanghai Jiao Tong University School of Medicine|Xinhua Hospital, Shanghai Jiao Tong University School of Medicine|Ruijin Hospital|RenJi Hospital|Eastern Hepatobiliary Surgery Hospital|Huashan Hospital July 2016 Phase 2
NCT02824458 Recruiting EGFR Tyrosine Kinase Inhibitors Plus VEGFR Inhibitors Sun Yat-sen University June 2016 Phase 3
NCT02740894 Completed Is Targeted Therapy Increasing Survival Inoperable Nonsmall Cell Lung Cancer With Spinal Metastasis ? Taipei Veterans General Hospital, Taiwan February 2016 --
NCT02347839 Recruiting Lung Cancer Sun Yat-sen University January 2016 Phase 2
NCT02588261 Recruiting Non-small Cell Lung Cancer (NSCLC) Astellas Pharma Global Development, Inc.|Astellas Pharma Inc November 2015 Phase 3

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Chemical Information

Download Gefitinib (ZD1839) SDF
Molecular Weight (MW) 446.90
Formula

C22H24ClFN4O3

CAS No. 184475-35-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 89 mg/mL (199.14 mM)
Ethanol 4 mg/mL (8.95 mM)
Water <1 mg/mL (<1 mM)
In vivo 5% DMSO+corn oil 2.5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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