Gefitinib (ZD1839)

Catalog No.S1025 Synonyms: Iressa

For research use only.

Gefitinib (ZD-1839, Iressa) 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. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.

Gefitinib (ZD1839) Chemical Structure

CAS No. 184475-35-2

Selleck's Gefitinib (ZD1839) has been cited by 586 publications

Purity & Quality Control

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Biological Activity

Description Gefitinib (ZD-1839, Iressa) 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. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.
Features A potent EGFR tyrosine kinase inhibitor.
Targets
Tyr1173 (NR6W cells) [1] Tyr1173 (NR6wtEGFR cells) [1] Tyr992 (NR6wtEGFR cells) [1] Tyr992 (NR6W cells) [1]
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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H1975 NGToVlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHxUmZKSzVyPUKxMlQ3OSEQvF2= MnXDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
HT NES3e5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HtXGlEPTB;MkGuOFM{OSEQvF2= M2TCUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
HUTU-80 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnZTWM2OD1{MT60N|M3KM7:TR?= M4faW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
PA-1 MnnUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1Hk[GlEPTB;MkGuNlc5PyEQvF2= NECwPWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw6OzlxJ{7TRW5ITVJ:L3G+
HOP-62 NEe0[4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHflUZdKSzVyPUKxMlI4QDRizszN NUe5ZmN1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNQTN7Lze+V2FPT0WUPD;hQi=>
GI-1 MkjHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1G3V2lEPTB;MkGuNVch|ryP NFfKZ4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw6OzlxJ{7TRW5ITVJ:L3G+
MC116 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfTRo5KSzVyPUKxMlA4OjNizszN MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-
A375 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmHLTWM2OD1{MT6wOVY4KM7:TR?= NFTQN4k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw6OzlxJ{7TRW5ITVJ:L3G+
IST-SL1 M4e1SGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7iTWM2OD1{MD63PFc6KM7:TR?= NWDob2RyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNQTN7Lze+V2FPT0WUPD;hQi=>
TE-5 MlTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrEbHc{UUN3ME2yNE44PDh{IN88US=> MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-
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TYK-nu NXG5Z4VCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;ydFFbUUN3ME2xPU45Ozd6IN88US=> NY\PcmVtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNQTN7Lze+V2FPT0WUPD;hQi=>
NCI-H650 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHuz[YFKSzVyPUG5Mlc2ODhizszN NYe2fXY3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNQTN7Lze+V2FPT0WUPD;hQi=>
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HuH-7 MnXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTF7Lke0NlEh|ryP MlO3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
NCI-N87 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LZd2lEPTB;MUmuOVk6OiEQvF2= MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly5N|kwLz6VQV7HSXI9N2F-
NCI-H1048 MmXwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\LeWlEPTB;MUmuNlMzPiEQvF2= M2K2SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
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D-263MG MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHrmVFBKSzVyPUG5MlAyPzJizszN M1\Mc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFk{QS9pPmPBUmdGWjxxYU6=
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OVCAR-8 MmXaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkG1TWM2OD1zOD65Nlc3KM7:TR?= NYDyO3hJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNQTN7Lze+V2FPT0WUPD;hQi=>
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MDA-MB-361 NW[4S3VLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1LreGlEPTB;MUiuOVU5QCEQvF2= MkLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMPVM6Nyd-U1HOS2VTRC:jPh?=
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Assay
Methods Test Index PMID
Western blot phospho-EGFR / phospho-ERK / phospho-SRC / phospho-AKT ; Cyclin D1/ p16 / p27 / pRb ; uc-caspase-9 / c-caspase-9 / uc-caspase-3 / c-caspase-3 / uc-PARP / PARP ; PPAR-γ 22586683 18559346 23102728 23409107
Immunofluorescence EGFR / LC3 ; PPAR-γ ; p-EGFR / β-catenin 31196210 23409107 23461856
Growth inhibition assay GI50 23409107
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]

Protocol (from reference)

Cell Research:

[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 Research:

[3]

  • Animal Models: Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.
  • Dosages: 100 mg/kg
  • Administration: Once daily by oral administration (0.1 mL/10 g body weight) for 14 days

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.

30mg/mL

Chemical Information

Molecular Weight 446.90
Formula

C22H24ClFN4O3

CAS No. 184475-35-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03292133 Recruiting Drug: EGF816|Drug: Gefitinib Lung Cancer Massachusetts General Hospital|Novartis October 31 2017 Phase 2
NCT03122717 Active not recruiting Drug: Gefitinib|Drug: Osimertinib Non-Small Cell Lung Cancer Dana-Farber Cancer Institute|AstraZeneca May 9 2017 Phase 1|Phase 2
NCT02932345 Completed -- EGFR Mutation Positive Advanced Non-small-cell Lung Cancer AstraZeneca October 31 2016 --
NCT02824458 Recruiting Drug: Apatinib|Drug: Gefitinib|Drug: Placebo EGFR Tyrosine Kinase Inhibitors Plus VEGFR Inhibitors Sun Yat-sen University June 2016 Phase 3
NCT02804100 Unknown status -- Carcinoma Non-Small-Cell Lung|Bronchial Neoplasms|Carcinoma Bronchogenic|Lung Diseases|Lung Neoplasms Wenzhou Medical University May 2016 --

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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Frequently Asked Questions

Question 1:
I try to dissolve Gefitinib (ZD1839) in 0.5% methylcellulose+0.2% Tween 80 for in vivo experiments. However, when I prepare the mixture, it forms precipitates. Exists another way to dissolve completely the compound?

Answer:
S1025 can be dissovled in both 5% DMSO+corn oil and 5% DMSO+30% PEG 300+5% Tween 80+ddH2O at 2.5 mg/ml clearly. It dissolves in DMSO not readily, please sonicate and warm it in water bath at about 45 degree, and dissolve it clearly first. Then add other solvent.

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