Multiple myeloma is a plasma cell malignancy that is susceptible to drugs targeting protein homeostasis such as thalidomide analogues and proteasome inhibitors. Thalidomide analogues modulate the activity of DDB1/CUL4 E3-ligase complexes to perturb substrate recognition and proteasomal degradation thereof. We hypothesised that the cellular pool of DDB1/CUL4 associated factors (DCAFs) may mediate other essential plasma cell processes and offer new targets for therapeutic intervention. Utilising B32B3, a previously disclosed DCAF1 kinase inhibitor as a template, we developed a series of analogues with enhanced anti-myeloma potency.