PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase.
作者： John J. Reiners , Jing-Yu Lee , Russell E. Clift , David T. Dudley , Scott P. Myrand
DOI: 10.1124/MOL.53.3.438
关键词: Cytosol 、 Ligand (biochemistry) 、 Biochemistry 、 IC50 、 Mitogen-activated protein kinase kinase 、 Kinase 、 Protein kinase A 、 Chemistry 、 Aryl hydrocarbon receptor 、 Receptor
摘要: PD98059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one] is a flavonoid and potent inhibitor of mitogen-activated protein kinase (MEK). Concentrations /=10 microM. In vivo exposure cultures to 95%) the dually phosphorylated forms extracellular signal-regulated (IC50 = 1 muM). Treatment with >/=1 muM either at time addition or up 48 hr before 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed in concentration-dependent manner accumulation induced steady state CYP1A1, CYP1B1, NQO1 mRNAs. The rat liver cytosol just TCDD binding 4 muM) aryl hydrocarbon receptor (AHR) transformation muM), as measured by sucrose gradient centrifugation electrophoretic mobility shift assays. Flavone flavanone, two closely related structural analogs PD98059, inhibited AHR IC50 values similar that obtained PD98059. However, neither analog was inhibiting MEK approximately 190 for both). These results suggest ligand functions an antagonist concentrations commonly used inhibit signaling processes entail activation.
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