Abstract
In the course of screening for anti-dementia agents from natural products, a beta-secretase (BACE1) inhibitor was isolated from the culture broth of Phellinus linteus and identified as hispidin. It showed an IC (50) value of 4.9 x 10 (-6) M and a Ki value of 8.4 x 10 (-6) M. The compound was a non-competitive inhibitor. Hispidin also inhibited a prolyl endopeptidase (IC (50) = 1.6 x 10 (-5) M, Ki = 2.4 x 10 (-5) M), but it was less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Cells, Cultured
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Endopeptidases
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Fungi*
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Humans
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Inhibitory Concentration 50
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Phytotherapy*
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Plant Extracts / administration & dosage
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Plant Extracts / pharmacology
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Plant Extracts / therapeutic use
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Pyrones / administration & dosage
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Pyrones / pharmacology*
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Pyrones / therapeutic use
Substances
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Enzyme Inhibitors
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Plant Extracts
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Pyrones
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE1 protein, human
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hispidin