The present invention provides pharmacological compounds including a peptide epoxy ketone protease inhibitor conjugated to a binding moiety that directs the peptide epoxy ketone protease inhibitor to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and a peptide epoxy ketone protease inhibitor. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the peptide epoxy ketone protease inhibitor.
