While the proteasome inhibitors bortezomib and carfilzomib licensed for treatment of relapsed multiple myeloma act by inhibiting the 20S catalytic core, RA190 irreversibly binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory cap of the 26S proteasome. Here, ADRM1 is linked to plasma cell myeloma.