Inhibition of epidermal growth factor‐induced DNA synthesis by tyrosine kinase inhibitors

Abstract
We prepared methyl 2,5‐dihydroxycinnamate as a stable analogue of erbstatin, a tyrosine kinase inhibitor. This analogue was about 4 times more stable than erbstatin in calf serum. It inhibited epidermal growth factor receptor‐associated tyrosine kinase in vitro with an IC50 of 0.15 . It also inhibited in situ autophosphorylation of epidermal growth factor receptor in A431 cells. Methyl 2,5‐dihydroxycinnamate was shown to delay the S‐phase induction by epidermal growth factor in quiescent normal rat kidney cells, without affecting the total amount ofDNA synthesis. The effect of erbstatin on S‐phase induction was smaller, possibly because of its shorter life time.