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In recent years it has become apparent that protein tyrosine kinases (PTKs) mediate proliferative signals as well as metabolic signals. 1 This realization promoted the hypothesis that PTK blockers (tyrphostins) can in prin-ciple become useful antiproliferative agents2, 3 and useful molecular tools to investigate signal transduction of PTKs. We have therefore synthesized low molecular weight PTK blockers2-4 which we demonstrated to be competitive in-hibitors of EGF receptor kinase and insulin receptor ki-nase5 and showed them to be effective blockers of EGF-dependent proliferation. 2, 3, 6 We have developed tyr-phostins which discriminate up to a factor of 103 in favor of EGF receptor kinase as compared to insulin receptor kinase. Furthermore, tyrphostins which were found to be effective in inhibiting EGF receptor kinase in vitro and EGF-dependent proliferation were indeed shown to inhibit the EGF-induced …