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Science 11 November 1988:
Vol. 242. no. 4880, pp. 933 - 935
DOI: 10.1126/science.3263702
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Articles

Science, Vol 242, Issue 4880, 933-935
Copyright © 1988 by American Association for the Advancement of Science

articles

Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors

P Yaish, A Gazit, C Gilon, and A Levitzki

Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.

A systematic series of low molecular weight protein tyrosine kinase inhibitors were synthesized; they had progressively increasing affinity over a 2500-fold range toward the substrate site of epidermal growth factor (EGF) receptor kinase domain. These compounds inhibited EGF receptor kinase activity up to three orders of magnitude more than they inhibited insulin receptor kinase, and they also effectively inhibited the EGF-dependent autophosphorylation of the receptor. The most potent compounds effectively inhibited the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on the EGF-independent proliferation of these cells. The potential use of tyrosine protein kinase inhibitors as antiproliferative agents is demonstrated.


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