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 microM) and p60c-src (IC50 = 65 microM) 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).
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Department of Experimental Surgery, Singapore General Hospital, Republic of Singapore. gesyeb@sgh.gov.sg
Zhang
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Cheng
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Mack
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D000081247:CSK Tyrosine-Protein Kinase; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005419:Flavonoids; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D011108:Polymers / Q000494:pharmacology; D059808:Polyphenols; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D047188:Chalcones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; C040918:butein; D002599:Chalcone; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C