Tyrphostins. 6. Dimeric benzylidenemalononitrile tyrophostins: potent inhibitors of EGF receptor tyrosine kinase in vitro

Journal of Medicinal Chemistry
A GazitA Levitzki

Abstract

Benzylidenemalononitrile (BMN) tyrphostins were previously found to be potent inhibitors of EGF receptor (EGFR) tyrosine kinase activity. Since these compounds were found to compete for the substrate and sometimes with the ATP site and since EGFR acts as a dimer, we prepared a series of dimeric tyrphostins. These dimeric tyrphostins were built from two BMN units linked by various spacers and designed to fit the dimeric cross-autophosphorylation signal transduction intermediate of the EGFR tyrosine kinases. Structure-activity relationship of these potent dimeric EGF receptor tyrosine kinase inhibitors is reported.

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Citations

Apr 1, 1999·Biotechnology and Bioengineering·S ShiA W Czarnik
Sep 5, 2002·International Journal of Cancer. Journal International Du Cancer·Giuseppina OrtuEyal Mishani
Dec 23, 2011·Journal of Chemical Biology·Erdem BangiMarc Hild
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Jul 6, 2004·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kazuyasu Nakaya
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Mar 10, 1999·The American Journal of Physiology·C Tertrin-ClaryF Ferré

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