A small molecule inhibitor of β-catenin/cyclic AMP response element-binding protein transcription

• DOI: 10.1073/pnas.0404875101
• Publication Date: 2004-08-17T01:08:46Z
• Authors: Katayoon H. Emami; Cu Nguyen; Hong Ma; Dae Hoon Kim; Kwang Won Jeong; Masakatsu Eguchi; Randall T. Moon; Jia-Ling Teo; Se Wong Oh; Hak Yeop Kim; Sung Hwan Moon; Jong Ryul Ha; Michael Kahn
• Keywords: Adenomatous polyposis coli

Inherited and somatic mutations in the adenomatous polyposis coli occur most colon cancers, leading to activation of β-catenin-responsive genes. To identify small molecule antagonists this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compounds that inhibit reporter. We identified ICG-001, down-regulates β-catenin/T cell factor signaling by specifically binding cyclic AMP response element-binding protein. ICG-001 selectively induces apoptosis but not normal cells, reduces vitro growth carcinoma is efficacious Min mouse nude xenograft models cancer.