Inhibition of oncogene product enzyme activity as an approach to cancer chemoprevention. Tyrosine-specific protein kinase inhibition by purpurogallin from Quercus sp. nutgall.
Inhibitors of oncogene product enzyme activity were sought as a prescreen for potential cancer chemopreventive agents. Purpurogallin, a polyphenol from Quercus sp. nutgall, was found to inhibit the tyrosine-specific protein kinase of the human erb-b oncogene product (epidermal growth factor receptor) for both autophosphorylation (IC50 = 27.5 microM) and phosphorylation of an exogenous substrate (IC50 = 45.3 microM). An examination of enzyme kinetics indicated that purpurogallin is a competitive inhibitor of both ATP (Ki = 54.9 microM for autophosphorylation, Ki = 33.9 microM for phosphorylation of exogenous substrate) and the tyrosine-containing acceptor substrate poly(glutamate, alanine, tyrosine) 6:3:1 (Ki = 83.7 microM).
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
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Abou-Karam
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Shier
D001567:Benzocycloheptenes / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation; D010944:Plants / Q000737:chemistry*
D001567:Benzocycloheptenes; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; C026133:purpurogallin