The degree of inhibition of protein tyrosine kinase activity by tyrphostin 23 and 25 is related to their instability.

Abstract

Tyrphostins, a series of compounds with hydroxy cis-cinnamonitrile backbone structures, are used as protein tyrosine kinase inhibitors to study signal transduction. While studying the inhibition of pp60c-src protein tyrosine kinase activity with tyrphostins 23 and 25 (3,4-di- and 3,4,5-trihydroxy cis-cinnamonitrile), we found the inhibitors to be quite unstable. The inhibition of pp60c-src activity corresponded to the formation of products derived from the parent tyrphostin compound. One of these isolated products was at least 10-fold more inhibitory to both pp60c-src and epidermal growth factor receptor kinase activity than the parent tyrphostin. The generation of compounds more inhibitory than the parent tyrphostin may explain the delayed inhibition reported with epidermal growth factor receptor kinase activity. Since these tyrphostins are unstable and form compounds more inhibitory towards protein tyrosine kinase activity, any results obtained with these compounds must be interpreted with caution.