10516 Background: Aberrant regulation of the Wnt pathway has been shown to be associated with breast cancer. We hypothesize that (1) increased co-activator interaction of CBP with nuclear β-catenin is associated with a breast cancer stem-cell phenotype, disease progression, drug resistance, relapse and metastasis, and (2) the usage of the co-activator p300 leads to forced differentiation of cancer stem cells rendering them sensitive to existing chemotherapeutics. Methods: We have developed ICG-001, a small molecule antagonist of the CBP/β-catenin interaction. Breast cancer cells (MDA-MB-231, MDA-MB-468, MCF-7) were treated with ICG-001 and investigated for changes in proliferation, invasiveness and drug resistance. RNA sequencing and qRT-PCR were used to evaluate gene-expression. CoIP and CHiP assays demonstrated CBP/β-catenin disruption and differential coactivator usage at specific gene promoters. Protein expression was assessed by FACS and Immunoblotting. Viability assays were done to determine drug-se...