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

FEBS Letters

Isshiki, Kunio²  Tajima, Hirohisa¹  Takeuchi, Tomio²  Hori, Takashi¹  Imoto, Masaya¹  Umezawa, Kazuo¹ 

[1] Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 Japan;Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku. Tokyo 141, Japan

关键词: Erbstatin;    Epidermal growth factor;    DNA synthesis;    Cell cycle;    (Normal rat kidney cell);   

DOI  :  10.1016/0014-5793(90)80102-O

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown