The disclosure provides methods of identifying and making compounds and pharmaceutical compositions containing the compounds that inhibit the interaction between MUC1 and an IKK. The disclosure also provides in vivo and in vitro methods of inhibiting such an interaction. Also embraced by the disclosure are in vitro and in vivo methods of inhibiting the IKK/NF-κB pathway in cells expressing MUC1. The compounds, compositions, and methods of the disclosure are generally useful in the treatment of various cancers, inflammatory (e.g., autoimmune disorders), and transplant rejection.