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Ref Type Journal Article
PMID (15314234)
Authors Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M
Title A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected].
Journal Proceedings of the National Academy of Sciences of the United States of America
Vol 101
Issue 34
Date 2004 Aug 24
Abstract Text 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.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ICG-001 ICG-001 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
ICG-001 ICG001|ICG 001 CTNNB1 Inhibitor 26 ICG-001 disrupts the interaction of CTNNB1 and c-AMP response element-binding protein, thereby preventing downstream CTNNB1 signaling to promote apoptosis (PMID: 15314234, PMID: 29332125, PMID: 32642722).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
APC inact mut colon cancer sensitive ICG-001 Preclinical Actionable In a preclinical study, ICG-001 decreased cell proliferation in colon cancer cell lines and in mouse models carrying APC inactivating mutations (PMID: 15314234). 15314234