Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Gefitinib [184475-35-2]
Referencia T1181-1g
embalaje : 1g
Marca : TargetMol
Contact local distributor :
Teléfono : +1 850 650 7790
Gefitinib
Catalog No. T1181 CAS 184475-35-2
Synonyms: ZD1839
Gefitinib (ZD1839) is an EGFR first-generation inhibitor with oral activity that inhibits the EGFR 19 Del and L858R mutations. Gefitinib has antitumor activity and is used for the treatment of EGFR-mutated non-small-cell lung cancers. Gefitinib administration RESULTS in the development of the EGFR C797S resistance mutation.
All TargetMol products are for research or drug registration purposes only and cannot be used for human consumption. We do not provide products or services to individuals. Please comply with the intended use and do not use TargetMol products for any other purpose in violation of laws and regulations.
Gefitinib, CAS 184475-35-2
| Pack Size | /USD | |
|---|---|---|
| 100 mg | In stock | |
| 500 mg | In stock | |
| 1 g | In stock | |
| 5 g | In stock | |
| 1 mL * 10 mM (in DMSO) | In stock |
Select Batch 
Purity: 100%
Purity: 100%
Purity: 100%
Purity: 100%
Purity: 100%
Purity: 99.92%
Contact us for more batch information
| Description | Gefitinib (ZD1839) is an EGFR first-generation inhibitor with oral activity that inhibits the EGFR 19 Del and L858R mutations. Gefitinib has antitumor activity and is used for the treatment of EGFR-mutated non-small-cell lung cancers. Gefitinib administration RESULTS in the development of the EGFR C797S resistance mutation. |
| Targets&IC50 | Tyr992:57 nM (NR6W cells), Tyr992:37 nM (NR6wtEGFR cells) , Tyr1173:37 nM (NR6wtEGFR cells), Tyr1173:26 nM (NR6W cells) |
| In vitro | METHODS: Twenty-three tumor cells were treated with Gefitinib for 72 h, and cell viability was measured by MTT. RESULTS: Only the PC9 cell line had an IC50 <1 μmol/L (highly sensitive), 14 cell lines had an IC50 >10 μmol/L (resistant), and the remaining 8 cell lines had an IC50 of 1-10 μmol/L (moderately sensitive). [1] METHODS: Tumor cells HT29, KB, Du145 and A549 were treated with Gefitinib (0.032-50 μM) for 2 h. EGF (0.1 μg/mL) was added five minutes prior to cell lysis, and the expression levels of target proteins were detected using Western Blot. RESULTS: Gefitinib produced a dose-dependent inhibition of EGFR autophosphorylation in all tumor cell lines. [2] |
| In vivo | METHODS: To detect anti-tumor activity in vivo, Gefitinib (3.125-200 mg/kg in 0.5% polysorbate 80) was administered orally to nude mice harboring tumors A431, Du145, or A549 once a day for seven to fifteen days. RESULTS: Gefitinib inhibited the growth of A431, Du145 or A549 tumors in a dose-dependent manner. [2] METHODS: To assay antitumor activity in vivo, Gefitinib (40 mg/kg once daily) or Gefitinib (200 mg/kg every five days) was administered by gavage for two weeks to athymic nude mice harboring the human lung cancer tumor H3255. RESULTS: Weekly treatment showed better inhibition than daily treatment. Compared with the daily dosing regimen, the weekly dosing regimen showed stronger inhibition of p-EGFR, p-ERK, and p-AKT. [3] |
| Cell Research | The human NSCLC H1299, H1975, A549, H460, GLC82, H460, and CALU-3 cell lines were provided by the American Type Culture Collection and maintained in RPMI-1640 supplemented with 10% FBS in a humidified atmosphere with 5% CO2. CALU-3 GEF-R is a cell line obtained in vitro as previously described. Briefly, over a period of 12 months, human CALU-3 lung adenocarcinoma cells were continuously exposed to increasing concentrations of gefitinib. The starting dose was the dose causing the inhibition of 50% of cancer cell growth (IC50; gefitinib, 1 μmol/L). The drug dose was progressively increased to 15 μmol/L in approximately 2 months, to 20 μmol/L after other 2 months, to 25 μmol/L after additional 2 months, and, finally, to 30 μmol/L for a total of 12 months. The established resistant cancer cell lines were then maintained in continuous culture with the maximally achieved dose of each TKI that allowed cellular proliferation (30 μmol/L for each drug) [2]. |
| Animal Research | Four- to 6-week old female balb/c athymic (nu+/nu+) mice were purchased from Charles River Laboratories. Mice were acclimatized for 1 week before being injected with cancer cells and injected subcutaneously with 107 H1299 and CALU-3 GEF-R cells that had been resuspended in 200 μL of Matrigel. When established tumors of approximately 75 mm3 in diameter were detected, mice were left untreated or treated with oral administrations of metformin (200 mg/mL metformin diluted in drinking water and present throughout the experiment), gefitinib (150 mg/kg daily orally by gavage), or both for the indicated time periods. Each treatment group consisted of 10 mice. Tumor volume was measured using the formula π/6 × larger diameter × (smaller diameter)2. Tumor tissues were collected from the xenografts and analyzed by Western blotting for the expression and activation of EGFR, AMPK, mitogen-activated protein kinase (MAPK), and S6 [2]. |
| Source | Natural Products > Apiaceae > Centella |
| Synonyms | ZD1839 |
| Molecular Weight | 446.9 |
| Formula | C22H24ClFN4O3 |
| CAS No. | 184475-35-2 |
Storage
Solubility Information
DMSO: 18.33 mg/mL (41.02 mM)
Ethanol: 4.5 mg/mL (10 mM)
References and Literature
1. Noro R, et al. Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation. BMC Cancer. 2006 Dec 6;6:277. 2. Wakeling AE, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. 2002 Oct 15;62(20):5749-54. 3. Zhang Q, et al. Effect of weekly or daily dosing regimen of Gefitinib in mouse models of lung cancer. Oncotarget. 2017 Aug 2;8(42):72447-72456. 4. Tan J, et al. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model. Oncotarget. 2017 Oct 19;8(58):98771-98781. 6. Dhar D, et al. Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell. 2018 Jun 11;33(6):1061-1077.e6. 8. Teng J F, Qin D L, Mei Q, et al. Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer[J]. Pharmacological Research. 2019: 104396. 9. . circSETD3 Contributes to Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer by Targeting the miR-520h/ABCG2 Pathway. Molecular Therapy-Nucleic Acids. 2020 10. Quan C, Chen Y, Wang X, et al. Loss of histone lysine methyltransferase EZH2 confers resistance to tyrosine kinase inhibitors in non-small cell lung cancer. cancer letters. 2020
Citations
1. Oeller M, Jaksch-Bogensperger H, Templin M, et al.Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation.International Journal of Molecular Sciences.2022, 23(24): 15782. 2. He S, Shi J, Zhou H H, et al.Lnc-ABCA12-8 confers acquired resistance to gefitinib in non-small cell lung cancer by regulating the alternative splicing of fibronectin 1 in the IIICS region.Cancer Gene Therapy.2022, 29(11): 1686-1696. 3. Wen C, Li Y, Huang Y, et al.CircSETD3 mediates acquired resistance to gefitinib in non-small lung cancer cells by FXR1/ECT2 pathway.The International Journal of Biochemistry & Cell Biology.2022: 106344. 4. Hu L, Liu Y, Fu C, et al.The Tumorigenic Effect of the High Expression of Ladinin-1 in Lung Adenocarcinoma and Its Potential as a Therapeutic Target.Molecules.2023, 28(3): 1103. 5. Chen J, Lei C, Nie D, et al.Inorganic arsenic exposure promotes malignant progression by HDAC6‐mediated down‐regulation of HTRA1.Journal of Applied Toxicology.2023 6. Jiao D, Chen Y, Liu X, et al.Targeting MET endocytosis or degradation to overcome HGF-induced gefitinib resistance in EGFR-sensitive mutant lung adenocarcinoma.Biochemical and Biophysical Research Communications.2023 7. Yang S, Yang S, Zhang H, et al. Targeting Na+/K+‐ATPase by berbamine and ouabain synergizes with sorafenib to inhibit hepatocellular carcinoma. British Journal of Pharmacology. 2021 8. Zhao X, Zhang N, Huang Y, et al. Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells in vitro and in vivo. Frontiers in Cell and Developmental Biology. 2021, 9: 947 9. Wang L, Liu X X, Yang Y M, et al. RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression. Cancer Cell International. 2021, 21(1): 1-18. 10. Shi J, Huang Y, Wen C, et al. Genome-wide identification and characterization of long non-coding RNAs involved in acquired resistance to gefitinib in non-small-cell lung cancer. Computational Biology and Chemistry. 2020, 87: 107288.
11. Zhao Deng,Chenbin Cui,Yanan Wang,Jiangjin Ni, et al. FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect on DSS-induced colitis via the Nrf2 pathway. Food & Function. 2020 12. Cao D, Chen D, Xia J N, et al. Artesunate promoted anti-tumor immunity and overcame EGFR-TKI resistance in non-small-cell lung cancer by enhancing oncogenic TAZ degradation. Biomedicine & Pharmacotherapy. 2022, 155: 113705. 13. Liu Y, Luo Y, Yan S, et al. CRL2KLHDC3 mediates p14ARF N-terminal ubiquitylation degradation to promote non-small cell lung carcinoma progression. Oncogene. 2022: 1-14 14. Kang J, Guo Z, Zhang H, et al. Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer. International Journal of Molecular Sciences. 2022, 23(18): 10382 15. Teng J F, Qin D L, Mei Q, et al. Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer. Pharmacological Research. 2019: 104396. 16. Shang J, Ning S, Chen Y, et al. MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. Acta Pharmacologica Sinica. 2021, 42(1): 120-131 17. Zheng P, Huang Z, Tong D C, et al. Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways. World Journal of Gastrointestinal Oncology. 2022, 14(2): 450 18. Yu J, Zhang L, Peng J, et al. Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochemical pharmacology. 2022, 195: 114864. 19. Yutang Huang,Yi Dai,Chunjie Wen,Shuai He,Jingjing Shi,Dezhang Zhao,Lanxiang Wu,Honghao Zhou circSETD3 Contributes to Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer by Targeting the miR-520h/ABCG2 Pathway. Molecular Therapy-Nucleic Acids. 2020 20. Liang J, Bi G, Sui Q, et al.Transcription factor ZNF263 enhances EGFR-targeted therapeutic response and reduces residual disease in lung adenocarcinoma.Cell Reports.2024, 43(2). 21. Shao J, Ye Z, Shen Z, et al.Chidamide improves gefitinib treatment outcomes in NSCLC by attenuating recruitment and immunosuppressive function of myeloid-derived suppressor cells.Biomedicine & Pharmacotherapy.2024, 173: 116306. 22. Hou X, Ai X, Liu Z, et al.Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus/enterocytes for effective oral absorption of shikonin and gefitinib.Drug Delivery and Translational Research.2024: 1-18. 23. Zhang D, Tian X, Wang Y, et al.Polyphyllin I ameliorates gefitinib resistance and inhibits the VEGF/VEGFR2/p38 pathway by targeting HIF-1a in lung adenocarcinoma.Phytomedicine.2024: 155690.
Related compound libraries
This product is contained In the following compound libraries：
Anti-Cancer Active Compound Library Tyrosine Kinase Inhibitor Library Anti-Cancer Drug Library Natural Product Library Natural Product Library for HTS Inhibitor Library Kinase Inhibitor Library FDA-Approved Kinase Inhibitor Library Anti-Cancer Clinical Compound Library Anti-Cancer Approved Drug Library
Related Products
Related compounds with same targets
Dose Conversion
You can also refer to dose conversion for different animals. More
In vivo Formulation Calculator (Clear solution)
Step One: Enter information below
Dosage
mg/kg Average weight of animals
g Dosing volume per animal
ul Number of animals
Step Two: Enter the in vivo formulation
% 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)，
Method for preparing in vivo formulation：Take μL DMSO master liquid, next add μL PEG300， mix and clarify, next add μL Tween 80，mix and clarify, next add μL ddH2O, mix and clarify.
Note:
Be sure to add the solvent(s) in order. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Calculator
bottom
Tech Support
Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.
Keywords
Gefitinib 184475-35-2 Angiogenesis Autophagy JAK/STAT signaling Tyrosine Kinase/Adaptors Tyrosine Kinases EGFR EGFR tyrosine kinase lung cancer breast cancer phosphorylation ZD1839 Inhibitor Apoptosis inhibit TAMs NSCLCs antitumour Epidermal growth factor receptor HER1 tumor metastasis ZD-1839 ZD 1839 ErbB-1 inhibitor