Butein, a specific protein tyrosine kinase inhibitor

Butein, a plant polyphenol, was shown to be a specific protein tyrosine kinase inhibitor. This compound inhibited not only the epidermal growth factor (EGF)-stimulated auto phosphotyrosine level of EGF receptor in HepG2 cells but also tyrosine-specific protein kinase activities of EGF receptor (IC50 = 65 mu M) and p60(c-src) (IC50 = 65 mu M) in vitro. The inhibition was competitive to ATP and non-competitive to the phosphate acceptor, poly (Glu, Ala, Tyr) 6:3:1 for EGF receptor tyrosine kinase. In contrast, butein non-significantly inhibited the activities of serine-and threonine-specific protein kinases, such as protein kinase C (PKC) and cAMP-dependent protein kinase (PKA). (C) 1998 Academic Press.