Gefitinib (ZD1839) 化学構造
分子量: 446.90

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Quality Control & MSDS

製品説明

  • Compare EGFR Inhibitors
    EGFR製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Gefitinib (ZD1839) は、NR6wtEGFRとNR6W細胞のTyr1173、Tyr992、Tyr1173とTyr992のためのEGFR阻害剤で、IC50 がそれぞれ 37 nM、 37nM、 26 nM 、57 nMです。
ターゲット Tyr1173 (NR6wtEGFR cells) Tyr992 (NR6wtEGFR cells) Tyr1173 (NR6W cells) Tyr992 (NR6W cells)
IC50 37 nM 37nM 26 nM 57 nM [1]
In vitro試験 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
KB NGHDdmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojaTWM2OD1yLkC1OEDPxE1? M3fjV|E3PTF4NEez
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COS7 M1i5[GZ2dmO2aX;uJGF{e2G7 NHnxfoE6PiEQvF2= NUDlTVd2UW6qaXLpeIlwdiCxZjDoeY1idiCMQVuyJHY3OTeIIH31eIFvfCCneIDy[ZN{\WR? MV[xO|E4QDd{Mh?=
A549 MWHDfZRwfG:6aXOgRZN{[Xl? NUfVVIMyQTZiaB?= Mn:1SG1UVw>? MVjJR|UxRTF|LkW5JO69VQ>? NIjvTm8yQDNzM{iwOy=>
K562 NHj6cldEgXSxdH;4bYMhSXO|YYm= MXe5OkBp MofxSG1UVw>? NGXYcllKSzVyPUmuN|Yh|ryP NF3ZbZQyQDNzM{iwOy=>
MDA-MB-231 MWDDfZRwfG:6aXOgRZN{[Xl? M2Oyb|k3KGh? NYO4dnVUTE2VTx?= MUnJR|UxRTN4Lk[xJO69VQ>? MnXUNVg{OTN6MEe=
MOLT4 NF7YcI5EgXSxdH;4bYMhSXO|YYm= NULoXXRUQTZiaB?= NYHtfFlSTE2VTx?= NInUbnhKSzVyPUG1MlAzKM7:TR?= MoPoNVg{OTN6MEe=
MCF7 NGOzTFBEgXSxdH;4bYMhSXO|YYm= NYPpWXdkPTBizszN MX63NkBp NXrGfZdoUUN3ME2xNk4xPSEQvF2= NInhV3MyQDd5MUixPS=>
BT474 M4L6PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXQXo84OiCq MVvBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEKWNEe0JINmdGy|IH;2[ZJmgHC{ZYPzbY5oKEWUQnKyJJdqfGhiRVO1NEBw\iByLkOg{txO NVPHNmFHOTlyMki0NlQ>
HN5 MlLrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTDO|IhcA>? NELWZpJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjOOUBk\WyuczDveoVz\XiycnXzd4lv\yCHR1\SJJdqfGhiRVO1NEBw\iByLkCxJO69VQ>? MV[xPVAzQDR{NB?=
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MCF7 MX MoPJSpVv[3Srb36gRZN{[Xl? NITlbGM{OCCvaX6= NI\QNZNKdmirYnn0bY9vKG:oIFLDVnAh\XiycnXzd4VlKHerdHigTWM2OCCxZjCxMlEh|ryP MXOxPVk{Ojl4MB?=
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Plasmodium falciparum NF3hcFNyUFSVIIDyc4ZqdGmwZzDmc5IhcW6qaXLpeI9zeyCxZjDQcIF{dW:maYXtJIZidGOrcHHyeY0heHKxbHnm[ZJifGmxbh?= M2DXPVIyQDF5MES1
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NCI-H292 M4PXSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHYd3c4OiCq NGftSJVFVVOR NVzVd|E3UUN3ME2wMlAzKM7:TR?= NIqxRWwzOTlzNkSzNy=>
A431 M3nzVWtqdmG|ZTDBd5NigQ>? M{TBflIhcA>? MUPEUXNQ MX;Jcohq[mm2aX;uJI9nKEWJRmKgdIhwe3Cqb4L5cIF1cW:wIHnuJGVITi2|dHnteYxifGWmIHj1cYFvKEF2M{Gge4l1cCCLQ{WwJI9nKDBwMECxJO69VQ>? MlWzNlIyODFzM{K=
MCF7 NHHOSXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvXNVAxyqEQvHevcWw> MWq0PEBp NXvDd4VFTE2VTx?= NU\z[4xzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4KGOnbHzzJI93\XKneIDy[ZN{cW6pIFXHSnIh\2WwZTD3bZRpKEmFNUCgc4YhOTJwMEWg{txO MX6yNlEyQTF|MB?=
BT474 NH;QZWZEgXSxdH;4bYMhSXO|YYm= NGTQdlQyOCEQvF2= MVu0PEBp Ml\6R5l1d3SxeHnjbZR6KGGpYXnud5Qhe2W{dX2td5Rien[nZDDoeY1idiCEVES3OEBk\Wyucx?= M3jRbVIzOTN6M{C4
MCF7 M4HoUWN6fG:2b4jpZ{BCe3OjeR?= NXfhTZJyOTBizszN MoGzOFghcA>? M2H2S2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KHOncoXtMZN1[XK4ZXSgbJVu[W5iTVPGO{Bk\WyuczDveoVzNWW6cILld5NqdmdiRYLiRlIh[2WubIO= NX3pO25uOjJzM{izNFg>
HCC827 MUjLbY5ie2ViQYPzZZk> M4S0[VAvOTJ3IN88US=> NVf3coxlOjRiaB?= MnH4SG1UVw>? NUe5eWZ[UW6qaXLpeIlwdiCxZjDFS2ZTKGSnbDDFO|Q3NUF5NUCgcZV1[W62IGmxNFY5KGG3dH;wbI9{eGixconsZZRqd25? NXWwdIFPOjJ|M{mzOFI>
HCC827 M2m0eWtqdmG|ZTDBd5NigQ>? M1e4ZlAvOTJ3IN88US=> NEXsN44zPCCq NYfBNIJ2TE2VTx?= Ml22TY5pcWKrdHnvckBw\iCHR1\SJIRmdCCHN{S2MWE4PTBibYX0ZY51NW2nZHnheIVlKEW{azDwbI9{eGixconsZZRqd25? MYSyNlM{QTN2Mh?=
HCC827 MnHWT4lv[XOnIFHzd4F6 MoXrNE4yOjVizszN MX:yOEBp NYHveYtKTE2VTx?= MYfJcohq[mm2aX;uJI9nKEWJRmKg[IVtKEV5NE[tRVc2OCCvdYThcpQudWWmaXH0[YQhSWu2IIDoc5NxcG:{eXzheIlwdg>? MnToNlI{Ozl|NEK=
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H460 NEXjbmlEgXSxdH;4bYMhSXO|YYm= MV[3NkBp MWXJR|UxRTVwNUmg{txO M2LrWFIzPzJ5NES5
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NCI-H2170 NFryRVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7tcGU6UUN3ME2yMlM1Pzh|IN88US=> MmTBV2FPT0WU
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SW780 M3P2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXnJR|UxRTR5Lk[zOVEh|ryP MWLTRW5ITVJ?
NCI-H1703 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnQbY1KSzVyPUS4MlM{PTJizszN NGPLV4JUSU6JRWK=
HCC1395 M3LVT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTR6Lke0N|Ih|ryP NFLNOoxUSU6JRWK=

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験 Gefitinib has entered in a phase II clinical trial in the treatment of non small cell lung cancer.
特集 A potent EGFR tyrosine kinase inhibitor.

プロトコル (参考用のみ)

細胞アッセイ: [1]

細胞株 NR6, NR6M and NR6W cells
濃度 0-2 μM
反応時間 72 hours
実験の流れ 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.

動物実験: [3]

動物モデル Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.
製剤 0.5% polysorbate
投薬量 100 mg/kg
投与方法 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 pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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

参考

化学情報

Download Gefitinib (ZD1839) SDF
分子量 446.90
化学式

C22H24ClFN4O3

CAS No. 184475-35-2
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 89 mg/mL (199.14 mM)
エタノール 4 mg/mL (8.95 mM)
<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.
化学名 N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine

カスタマーフィードバック (11)


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Source Mol Syst Biol , 2011, 7, 486. Gefitinib (ZD1839) purchased from Selleck
Method qPCR analysis
Cell Lines glioblastoma cell lines
Concentrations 5 μM, 50 ng/ml
Incubation Time 6 h
Results We perturbed the activity of the EGFR by activating it using one of its ligands (EGF) and inhibiting it with a selective EGFR inhibitor (Gefitinib). As readout, we measured the transcriptional effect on SOCS2 (a modulator of STAT signaling), NR2E1(also known as TLX , a transcription factor believed to be important for neural stem cell renewal), yielding results compatible with a coupling between hub perturbation and transcriptional response.

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Source Oncogene, 2010, 30, 737-750. Gefitinib (ZD1839) purchased from Selleck
Method Western blot
Cell Lines MEFs
Concentrations 1 μM
Incubation Time 48 h
Results We found that gefitinib, a specific EGFR inhibitor, almost completely recapitulated the results obtained by genistein (Figure a). Consistent with these results, we observed increased EGFR phosphorylation within 2 days of RECK depletion , with insignificant change in its protein amount (Figure b).

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Source Carcinogenesis, 2010, 31, 1948–1955 . Gefitinib (ZD1839) purchased from Selleck
Method Luciferase assay
Cell Lines LNCaP-AI cells, LNCaP cells
Concentrations 20 μM
Incubation Time 24 h
Results EGF significantly stimulates the promoter activity of sPLA2-IIa gene in both LNCaP and LNCaP-AI cells (shown in LNCaP-AI cells), whereas Gefitinib and other inhibitors all tested downregulated the promoter activity both at the basal level (shown in LNCaP cells) and in response to EGF stimulation (shown in LNCaP-AI cells)

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Source Carcinogenesis, 2010, 31, 1948–1955. Gefitinib (ZD1839) purchased from Selleck
Method ELISA
Cell Lines LNCaP-AI cells
Concentrations 20 μM
Incubation Time 24 h
Results Lapatinib, LY294002 and Bortezomib significantly inhibited sPLA2-IIa secretion, whereas Erlotinib, Gefitinib and CI-1033 had a moderate effect in LNCaP-AI cells .

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Source J Immunother, 2011, 34(4), 372-81. Gefitinib (ZD1839) purchased from Selleck
Method Cytotoxicity assay
Cell Lines NK-92 cells/ lung cancer cells
Concentrations 10 μM
Incubation Time 24 h
Results Susceptibility of lung cancer cells to cytolytic activity of NK cells was significantly increased by treatment with EGFR inhibitors (erlotinib/gefitinib) and was reversed by blocking step using mAb against NKG2D before the assay in all lung cancer cells.

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Source Antiviral Res, 2010, 89, 64-70. Gefitinib (ZD1839) purchased from Selleck
Method Proliferation assay, Plaque reduction test, Western blot, Real-time PCR
Cell Lines Hep2 cells
Concentrations 0.01-1000 μM
Incubation Time
Results While for Gefitinib concentrations between 100 μM and 0.01 μM the proliferation rate was almost 100% of the controls, only at concentrations of 1000 μM a slight (24%) decline in proliferation was observed (Fig.A). IC50 values of Gefitinib for plaque size reduction were calculated by dividing plaque size by total size of one tissue culture plate well for each compound concentration. A non-linear regression fit curve analysis from the calculated values revealed for plaque size reduction an IC50 value of 4.93μM for Gefitinib(Fig. B).The analysis of phosphorylated EGFR and of the downstream signaling kinases ERK1/2 in cell lysates of the assay confirmed the dose dependency of the antiviral effect of Gefitinib. Kinase activ-ities were completely suppressed at concentrations above 1μM as determined by Western blot analysis. VACV proteins were not detectable between 10 μM and 100 μM in Western blot analysis anymore (Fig. C).

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Source Antiviral Res, 2010, 89, 64-70. Gefitinib (ZD1839) purchased from Selleck
Method Immunofluorescence
Cell Lines Hep2 cells
Concentrations 0.01-1000 nM
Incubation Time 96 h
Results As shown in Fig. A, an immunofluorescent staining of a plaque reduction test was performed 96 h after viral infection. VACV infected cells were treated with 1000 μM, 1 μM or 0.01 μM Gefitinib and compared to uninfected cells after 96 h incubation. At concentrations of 1000 μM Gefitinib virus induced plaques were rarely found in cell culture and infected cells only could be identified by fluorescent staining of orthopoxvirus proteins (green) but not by light microscopy. At this Gefitinib concentration EGFR phosphorylation was completely suppressed in the cells and even the uninfected, untreated control cells show a stronger pEGFR signal (control, red). Occasionally found plaques, visible by flourescence microscopy only, showed a very compact shape with minimal disruption in its center. At the lower Gefitinib concentrations plaques showed an increasing number of infected and pEGFR positive cells (merge, yellow) and a surround-ing small zone of solely pEGFR positive cells (red). The lower the Gefitinib concentration the more plaques with a disrupted center were observed (1μM and 0.01μM). Most of the cells localized in the center of the plaque were positive for orthopoxvirus infection but negative for pEGFR ( Fig. B).

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Source Mol Biosyst, 2011, 7, 3223-33. Gefitinib (ZD1839) purchased from Selleck
Method Immunoprecipitation/Western blotting
Cell Lines
Concentrations 5 μM
Incubation Time 0-1 h
Results In the presence of the EGFR tyrosine kinase inhibitor Z D1839 (Iressa) revealed that the observed increase in binding between PCM1 and Azi1 is specific to EGFs timulation and requires E GFR activation.

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Source Int J Proteomics , 2011, 215496. Gefitinib (ZD1839) purchased from Selleck
Method CEER assay
Cell Lines H358 cell line
Concentrations 0.01-10 μM
Incubation Time 4 h
Results HER1 and/or HER2 pathway-activated cell lines, H358 , had their activation blocked by the HER1/2 kinase inhibitors Gefitinib.

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Source 2010, Dr. Zhang of Tianjin Medical University. Gefitinib (ZD1839) purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-5 nM
Incubation Time 24 h
Results

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Source 2010, Dr. Vicky Tin from University of Hong Kong. Gefitinib (ZD1839) purchased from Selleck
Method MTT assay
Cell Lines H1299 cells, H358 cells, H25 cells, HCC827 cells
Concentrations 0-400 nM
Incubation Time 72 h
Results

文献中の引用 (85)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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