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10g |
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Other Sizes |
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Purity: ≥98%
Targets |
Tyr1173 (IC50 = 26 nM); Tyr1173 (IC50 = 37 nM); Tyr992 (IC50 = 37 nM); Tyr992 (IC50 = 57 nM)
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ln Vitro |
Gefitinib effectively inhibits all EGFR tyrosine phosphorylation sites in cell lines that express EGFR, including NR6, NR6M, and NR6W cell lines, as well as high and low-EGFR-expressing cell lines. Tyr992 and Tyr1173, two phosphorylation sites, are less sensitive and require greater concentrations of Gefitinib to inhibit. With an IC50 of 27 nM, gefitinib efficiently prevents PLC-γ phosphorylation in NR6W cells. PLC-γ phosphorylation is low in the NR6wtEGFR and NR6M cell lines, but it is more resistant to gefitinib inhibition in the latter, with IC50 values of 43 nM and 369 nM, respectively. Gefitinib inhibits Akt phosphorylations in the low-EGFR- and EGFRvIII-expressing cell lines, with IC50 values of 220 and 263 nM, respectively. When administered at doses ranging from 0.1 to 0.5μM, gefitinib significantly promotes NR6M cell colony formation as opposed to inhibiting it. On the other hand, Gefitinib totally prevents NR6M colony formation at a concentration of 2 μM. In both the high- and low-EGFR-expressing cell lines, gefitinib quickly and dose-dependently inhibits EGFR and ERK phosphorylation for up to 72 hours following EGF stimulation.[1] These EGF-driven untransformed MCF10A cells grow monolayerically when exposed to gefitinib, with an IC50 of 20 nM. [2] When paired with irradiation, Gefitinib (0.2 μM and 0.5 μM) significantly inhibited the growth of LoVo cells in comparison to radiation alone.[3]
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ln Vivo |
Gefitinib (100 mg/kg) enhances radiation therapy's anti-tumor efficaciousness in LoVo tumor xenografts.[3] When established human GEO colon cancer xenografts are given to nude mice bearing these tumors, gefitinib treatment results in a reversible dose-dependent inhibition of tumor growth, as GEO tumors eventually resume the growth rate of controls.[4]
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Enzyme Assay |
Gefitinib hydrochloride is an inhibitor with an IC50 value of 2-37 nM in NR6wtEGFR cells that selectively binds to and inhibits the EGFR tyrosine kinase. With an IC50 of 27 nM, gefitinib efficiently prevents PLC-γ phosphorylation in NR6W cells. PLC-γ phosphorylation is low in the NR6wtEGFR and NR6M cell lines, but it is more resistant to gefitinib inhibition in the latter, with IC50 values of 43 nM and 369 nM, respectively. Gefitinib inhibits Akt phosphorylations in the low-EGFR- and EGFRvIII-expressing cell lines, with IC50 values of 220 and 263 nM, respectively.
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Cell Assay |
Exponentially growing cells, such as NR6, NR6M, NR6M, and NR6W cells, are seeded in 96-well plates at a density of 2000 cells/well, allowed to adhere, and then washed in PBS before being incubated overnight in medium containing 0.5% FCS. After that, cells are exposed to different concentrations (0–2 μM) of either gefitinib or the solute controls, DMSO and EGF. Since NR6wtEGFR and NR6W cells can proliferate best at a known EGF concentration, 10 nM and 0.1 nM EGF, respectively, are added to NR6wtEGFR and NR6W cells. NR6 and NR6M cells do not receive additional EGF. An MTT proliferation assay is used to quantify the number of cells after 72 hours.
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Animal Protocol |
Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.
100 mg/kg Once daily by oral administration (0.1 mL/10 g body weight) for 14 days |
References | |
Additional Infomation |
Gefitinib is a member of the class of quinazolines that is quinazoline which is substituted by a (3-chloro-4-fluorophenyl)nitrilo group, 3-(morpholin-4-yl)propoxy group and a methoxy group at positions 4,6 and 7, respectively. An EGFR kinase inhibitor used for the treatment of non-small cell lung cancer. It has a role as an epidermal growth factor receptor antagonist and an antineoplastic agent. It is an aromatic ether, a member of monochlorobenzenes, a member of monofluorobenzenes, a secondary amino compound, a tertiary amino compound, a member of quinazolines and a member of morpholines.
Gefitinib (originally coded ZD1839) is a drug used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib (marketed as Tarceva), gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa. Gefitinib is a Kinase Inhibitor. The mechanism of action of gefitinib is as a Protein Kinase Inhibitor. Gefitinib is a selective tyrosine kinase receptor inhibitor used in the therapy of non-small cell lung cancer. Gefitinib therapy is associated with transient elevations in serum aminotransferase levels and rare instances of clinically apparent acute liver injury. Gefitinib is a natural product found in Penicillium brocae with data available. Gefitinib is an anilinoquinazoline with antineoplastic activity. Gefitinib inhibits the catalytic activity of numerous tyrosine kinases including the epidermal growth factor receptor (EGFR), which may result in inhibition of tyrosine kinase-dependent tumor growth. Specifically, this agent competes with the binding of ATP to the tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and resulting in inhibition of signal transduction. Gefitinib may also induce cell cycle arrest and inhibit angiogenesis. (NCI04) A selective tyrosine kinase inhibitor for the EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) that is used for the treatment of locally advanced or metastatic NON-SMALL CELL LUNG CANCER. Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells. Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation. Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib. Biological Half-Life is 48 hours [IV administration] |
Molecular Formula |
C22H24CLFN4O3
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Molecular Weight |
446.90
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Exact Mass |
446.15
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Elemental Analysis |
C, 59.13; H, 5.41; Cl, 7.93; F, 4.25; N, 12.54; O, 10.74
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CAS # |
184475-35-2
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Related CAS # |
184475-35-2;857091-32-8; 184475-56-7; 184475-55-6; 1173976-40-3; 1173976-40-3; 1228664-49-0
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PubChem CID |
123631
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Appearance |
White solid powder
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Density |
1.3±0.1 g/cm3
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Boiling Point |
586.8±50.0 °C at 760 mmHg
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Melting Point |
119-120°C
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Flash Point |
308.7±30.1 °C
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Vapour Pressure |
0.0±1.6 mmHg at 25°C
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Index of Refraction |
1.621
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LogP |
4.11
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tPSA |
68.74
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SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
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InChi Key |
XGALLCVXEZPNRQ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C22H24ClFN4O3/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)
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Chemical Name |
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
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Synonyms |
Gefitinib; ZD-1839; ZD1839; ZD 1839; Brand name: Iressa
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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 |
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 | 2.2376 mL | 11.1882 mL | 22.3764 mL | |
5 mM | 0.4475 mL | 2.2376 mL | 4.4753 mL | |
10 mM | 0.2238 mL | 1.1188 mL | 2.2376 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. td> |
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. td> |
Effects of the combination treatment of metformin and gefitinib on NSCLC tumor xenografts.Clin Cancer Res.2013 Jul 1;19(13):3508-19. td> |
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