Gefitinib

Female nude mice (cba nu/nu) aged 8–10 weeks are intra-dermal injected with LoVo cells.

N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine

0-2 uM

100 mg/kg

0.5% polysorbate

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-gamma, with IC50 of 27nM, in NR6W cells. The NR6wtEGFR and NR6M cell lines has low levels of PLC-gamma 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 0.5uM significantly facilitates, rather than abrogates, colony formation of NR6M cells. However, at a concentration of 2 uM 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 uM and 0.5 uM) with irradiation lead to a significant growth inhibition in LoVo cells, compared with radiation alone.. [3]

72 hours

446, 9

Data from [Int J Proteomics , 2011, 2011, Article ID 215496], Gefitinib (Iressa)purchased from Selleck, Inhibition of signaling pathway activation in lung tumor cell lines by kinase inhibitors. Lung tumor cells were cultured in 10% FBS until reaching 80% confluence and then the cells were starved in serum-free medium for overnight, followed by 4-hour treatment with the inhibitors. Cell lysates were then prepared and used for determination of the pathway activation signals by the CEER assay.

DMSO 89 mg/mL, Water <1 mg/mL, Ethanol 4 mg/mL