Gefitinib (ZD1839)

Gefitinib (ZD-1839)は一種のEGFR阻害剤で、NR6wtEGFRとNR6Wの細胞中のTyr1173、Tyr992、Tyr1173とTyr992に作用する時のIC50値が37 nM、37nM、26 nMと57 nMにそれぞれ分かれることです。

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Gefitinib (ZD1839) 化学構造
分子量: 446.90

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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 (ZD-1839)は一種のEGFR阻害剤で、NR6wtEGFRとNR6Wの細胞中のTyr1173、Tyr992、Tyr1173とTyr992に作用する時のIC50値が37 nM、37nM、26 nMと57 nMにそれぞれ分かれることです。
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
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NCI-H2052 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTLO3NbUUN3ME20OU46ODJ5IN88US=> NHqwWpJUSU6JRWK=
SW684 NULrZpZZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU\CV5FqUUN3ME20O{4xODhzIN88US=> M1PvbHNCVkeHUh?=
HCC1569 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPCTWM2OD12Nz6xOlU5KM7:TR?= M3vhNnNCVkeHUh?=
KGN MlLXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvBTWM2OD12Nz6zN|EyKM7:TR?= MnzyV2FPT0WU
LCLC-103H NHjPbFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDpUnZUUUN3ME20O{41PDB2IN88US=> NWrCNnVWW0GQR1XS
SW780 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LafmlEPTB;NEeuOlM2OSEQvF2= NV\x[mFjW0GQR1XS
NCI-H1703 NEXxXo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPRTWM2OD12OD6zN|UzKM7:TR?= NXvaVVhlW0GQR1XS
HCC1395 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rIN2lEPTB;NEiuO|Q{OiEQvF2= M{DtRXNCVkeHUh?=

... 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 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 89 mg/mL (199.14 mM)
Ethanol 4 mg/mL (8.95 mM)
Water <1 mg/mL
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

文献中の引用 (91)

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.

技術サポート&よくある質問(FAQ)

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