A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected].
basic_science · Level V
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- Record sourced from PubMed, PMID 15314234.
- Also identified by PMC identifier 515116.
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Abstract
Inherited and somatic mutations in the adenomatous polyposis coli occur in most colon cancers, leading to activation of beta-catenin-responsive genes. To identify small molecule antagonists of this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compounds that inhibit a beta-catenin-responsive reporter. We identified ICG-001, a small molecule that down-regulates beta-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells, and is efficacious in the Min mouse and nude mouse xenograft models of colon cancer.
Medical subject headings
- Antineoplastic Agents
- Bridged Bicyclo Compounds, Heterocyclic
- Cyclic AMP Response Element-Binding Protein
- Cytoskeletal Proteins
- Gene Expression Regulation
- Pyrimidinones
- Trans-Activators
- Transcription, Genetic