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- W1969967988 abstract "Given the key role of Ras in the mitogenic signaling by receptor tyrosine kinases, several targets upstream of Ras may prove to be excellent targets for drugs in the treatment of cancer caused by oncogenic tyrosine kinases. CGP78850 is a potent competitor of Grb2 SH2-phosphopeptide interactions. This inhibitor has been obtained by rational drug design and is specific toward the Grb2 SH2 vs. other SH2 domains and the PTB domain of SHC in vitro. Accordingly, CGP78850 blocks epidermal growth factor receptor (EGFR)-Grb2 and Shc-Grb2 interactions in living cells. It also inhibits the growth of cells transformed by receptor tyrosine kinases, which transmit a proliferative signal through Grb2 to Ras, but not cells transformed by oncogenic Raf or cells that contain activating Ras mutations. Moreover, our results demonstrate that, in cells overexpressing receptor tyrosine kinases, such as the EGFR, Grb2 SH2 inhibitors induce expression of the cell cycle inhibitors p21Waf1/Cip1/CAP1 and p27Kip1 and reverse transformation. Int. J. Cancer 83:235–241, 1999. © 1999 Wiley-Liss, Inc." @default.
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- W1969967988 date "1999-10-08" @default.
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- W1969967988 title "Selective GRB2 SH2 inhibitors as anti-Ras therapy" @default.
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- W1969967988 doi "https://doi.org/10.1002/(sici)1097-0215(19991008)83:2<235::aid-ijc15>3.0.co;2-b" @default.
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