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KMID : 0613820110210030349
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Journal of Life Science
2011 Volume.21 No. 3 p.349 ~ p.357
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Novel Quinazoline Derivatives Targeting on EGFR Kinase Mediated Signal Pathway in A431 Human Epidermoid Carcinoma Cells
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Jeong Chul-Woo
Son Byeng-Wha
Ha Jae-Du
Kim Kun-Do
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Abstract
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Inhibitors of EGFR (epidermal growth factor receptor) kinase activity may prove useful to therapeutically intervene in cancer and to treat other proliferative diseases. In this study, we investigated the inhibitive effects of two compounds named 63013 and 63033 possess a [1,4]-dioxino quinazoline structure that links the alkoxy side chains together and their structural characteristics are considered to allow better solubility than the dialkoxyquinazoline derivatives. The EGFR kinase activities of A431 human epidermoid carcinoma cells, stimulated by EGF were inhibited by treatment with 63013 and 63033 in a dose-dependent manner respectively. Consistent with the compound-mediated EGFR kinase suppression, the major EGF-related downstream target molecules, such as MEK1/2, MAPK p44/42, AKT and STAT3, were also suppressed by both compounds. Interestingly, both compounds led to cell growth inhibition at a lower concentration than that of Gefitinib (Iressa®). Collectively, our study showed that both compounds may have good therapeutic potential as an EGFR kinase specific inhibitor to treat EGFR-related diseases.
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KEYWORD
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EGFR kinase, Gefitinib (Iressa®), MEK1/2, AKT, STAT3
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