| Size | Price | Stock | Qty |
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| 500mg |
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Purity: ≥98%
Gefitinib hydrochloride, the HCl salt of Gefitinib (formerly also known as ZD1839 or trade name: Iressa), is a potent and orally-bioavailable 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 exhibits anti-angiogenic activities in a wide range of human tumor types, including head and neck, prostate, breast, ovarian, colon, small-cell lung and non-small-cell lung cancer. In May 2003, the FDA approved Gefitinib for non-small cell lung cancer (NSCLC). It was approved as monotherapy for the treatment of patients with locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel chemotherapies. i.e. as a third-line therapy.
| Targets |
EGFR tyrosine kinase
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| ln Vitro |
After long-term exposure of EGFRvIII-expressing cells, gefitinib (0.01-0.1 mM) increases the phosphotyrosine load of the receptor, increases signaling to ERK, and stimulates proliferation and anchorage-independent growth. This effect is likely caused by the induction of EGFRvIII dimerization. Conversely, EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation, and anchorage-independent growth are all markedly reduced by gefitinib (1-2 mM)[1]. With an IC50 of 20 nM, gefitinib (ZD1839) prevents these EGF-driven untransformed cells from growing monolayer[2]. With an IC50 of 2 μM, gefitinib inhibits the growth of GLC82 and CALU-3 cells[3].
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| ln Vivo |
When metformin and gefitinib (150 mg/kg, po) are given to nude mice containing H1299 or CALU-3 GEF-R cells that are cultured subcutaneously as tumor xenografts, the tumor growth is significantly reduced[3]. While gefitinib therapy attenuates fibrotic lung remodeling due to the reduction of lung fibroblast proliferation, it increases lung inflammation in irradiated rats, including inflammatory cell infiltration and pro-inflammatory cytokine expression[4].
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| Cell Assay |
Purpose: EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) have been found to be effective against lung cancer, but clinical resistance to these agents has developed as their usage has increased. Metformin is a widely used antidiabetic drug and also displays significant growth-inhibitory and proapoptotic effects in several cancer models, alone or in combination with chemotherapeutic drugs.
Experimental design: The effects of gefitinib, a selective EGFR-TKI, and metformin on a panel of non-small cell lung cancer (NSCLC) cell lines were assessed by using MTT, bromide assay, flow cytometry, anchorage-independent growth, coimmunoprecipitation, and Western blot analysis. Results: The combination of metformin with gefitinib induced a strong antiproliferative and proapoptotic effect in NSCLC cell lines that harbored wild-type LKB1 gene. Treatment with metformin as single agent, however, induced an activation and phosphorylation of mitogen-activated protein kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. The inhibition of EGFR phosphorylation and of downstream signaling by adding gefitinib to metformin treatment abrogated this phenomenon and induced a strong apoptotic effect in vitro and in vivo. Conclusions: Metformin and gefitinib are synergistic in LKB1 wild-type NSCLC cells. However, further studies are required to investigate better the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecular targeted agents.[4] |
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| References |
[1]. 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.
[2]. Pedersen MW, et al. Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br J Cancer. 2005 Oct 17;93(8):915-23. [3]. Moasser MM, et al. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 2001 Oct 1;61(19):7184-8. [4]. Morgillo F, et al. Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3508-19. [5]. Miyake K, et al. Epidermal growth factor receptor-tyrosine kinase inhibitor (gefitinib) augments pneumonitis, but attenuates lung fibrosis in response to radiation injury in rats. J Med Invest. 2012;59(1-2):174-85 |
| Molecular Formula |
C22H24N4O3FCL.HCL
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|---|---|
| Molecular Weight |
483.3633
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| Exact Mass |
482.1287
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| CAS # |
184475-55-6
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| Related CAS # |
Gefitinib;184475-35-2
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| PubChem CID |
19077490
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| Appearance |
Typically exists as white to off-white solids at room temperature
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| Boiling Point |
607.7ºC at 760 mmHg
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| Vapour Pressure |
4.9E-15mmHg at 25°C
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| LogP |
5.09
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| tPSA |
68.74
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| SMILES |
ClC1=C(C=CC(NC2=NC=NC3=C2C=C(C(OC)=C3)OCCCN4CCOCC4)=C1)F.[H]Cl
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| InChi Key |
QUINXWLATMJDQF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24ClFN4O3.ClH/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15;/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27);1H
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| Chemical Name |
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;hydrochloride
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| Synonyms |
ZD1839 HCl; ZD 1839 HCl; ZD-1839 HCl; Gefitinib HCl; trade name: Iressa.Gefitinib hydrochloride; 184475-55-6; gefitinib hcl; Gefitinib (hydrochloride); ZD-1839 hydrochloride; Gefitinib hydrochloride salt; N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;hydrochloride; 4-Quinazolinamine,N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-,monohydrochloride;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0689 mL | 10.3443 mL | 20.6885 mL | |
| 5 mM | 0.4138 mL | 2.0689 mL | 4.1377 mL | |
| 10 mM | 0.2069 mL | 1.0344 mL | 2.0689 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A, effect of metformin (MET) alone and in combination with gefitinib (GEF) on cell proliferation, on anchorage-independent growth ability of NSCLC cell lines, and on the induction of apoptosis in CALU-3, CALU-3 GEF-R, and H1299 cell lines.Clin Cancer Res.2013 Jul 1;19(13):3508-19. |
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Effects on the downstream pathway by combined treatment of metformin and gefitinib. Western blotting of EGFR, MAPK, AKT p70S6K, and S6 activation following treatment with the indicated concentration of metformin and gefitinib in CALU-3 and CALU-3 GEF-R cell lines. β-Actin was included as a loading control.Clin Cancer Res.2013 Jul 1;19(13):3508-19. |
Effects of the combination treatment of metformin and gefitinib on NSCLC tumor xenografts.Clin Cancer Res.2013 Jul 1;19(13):3508-19. |
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