product name Gefitinib (ZD1839)
Description: Gefitinib, also known as ZD1839 or 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.
References: Br J Cancer. 2005;93(8):915-23.; Br J Cancer. 2002; 86(7): 1157–1161.; Clin Cancer Res. 2000;6(12):4885-92.
446.90
Formula
C22H24ClFN4O3
CAS No.
184475-35-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 89 mg/mL (199.1 mM)
Water: <1 mg/mL
Ethanol: 4 mg/mL (9.0 mM)
Solubility (In vivo)
5% DMSO+corn oil: 2.5 mg/mL
Synonyms
ZD1839
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19415980
| In Vitro |
In vitro activity: 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. Gefitinib is the monolayer growth of these EGF-driven untransformed MCF10A cells with an IC50 of 20 NM. 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. Kinase Assay: Cell Assay: 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. |
|---|---|
| In Vivo | Gefitinib (100 mg/kg) improves the anti-tumor effect of radiotherapy in LoVo tumor xenografts. 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. |
| Animal model | Nude mice (cba nu/nu) are intra-dermal injected with LoVo cells. |
| Formulation & Dosage | Dissolved in 0.5% polysorbate; 100 mg/kg; Oral gavage |
| References | Br J Cancer. 2005 Oct 17;93(8):915-23.; Br J Cancer. 2002 Apr 8; 86(7): 1157–1161.; Clin Cancer Res. 2000 Dec;6(12):4885-92. |
