The identification of novel therapeutic regimens for Imatinib resistant CML is a critical issue. This work demonstrates that the ability of the small molecule ICG-001 to block the CBP/-catenin interaction in addition to the CBP/β-catenin interaction may be clinically significant in the treatment of cancers, including CML, in which -catenin substitutes for reduced nuclear β-catenin, either due to genetic deletion or pharmacologic reduction of nuclear β-catenin.