Abstract
We designed and synthesized a series of indole-2-amide-based compounds that antagonize interaction between the Dishevelled (Dvl) PDZ domain and a peptide derived from the natural PDZ ligand Frizzled-7 (Fz7). These compounds inhibit Tcf-mediated transcription activated by exogenous Dvl via the biochemical antagonism. We confirmed tumor cell-selective activation of caspases by these compounds.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
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Adaptor Proteins, Signal Transducing / metabolism
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Apoptosis / drug effects
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Combinatorial Chemistry Techniques
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Dishevelled Proteins
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology*
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Models, Molecular*
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Molecular Structure
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PDZ Domains / drug effects
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Phosphoproteins / antagonists & inhibitors*
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Phosphoproteins / metabolism
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Structure-Activity Relationship
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TCF Transcription Factors / drug effects
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TCF Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Wnt Proteins / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Amides
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Dishevelled Proteins
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Indoles
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Phosphoproteins
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TCF Transcription Factors
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Wnt Proteins