Abstract
In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Biological Products / chemistry*
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Cell Line
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Dicarboxylic Acids / chemistry*
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Dicarboxylic Acids / isolation & purification
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Dicarboxylic Acids / pharmacology
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Dimerization
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Homeodomain Proteins / antagonists & inhibitors*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Immobilized Proteins / antagonists & inhibitors
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Immobilized Proteins / metabolism
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Mice
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Myxomycetes / chemistry
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Naphthoquinones / chemistry*
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Naphthoquinones / isolation & purification
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Naphthoquinones / pharmacology
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Pyrroles / chemistry*
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Pyrroles / isolation & purification
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Pyrroles / pharmacology
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Biological Products
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Dicarboxylic Acids
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Hes1 protein, mouse
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Homeodomain Proteins
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Immobilized Proteins
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Naphthoquinones
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Pyrroles
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Recombinant Proteins
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Transcription Factor HES-1
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lindbladione
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lycogaric acid A