with different pre-treatments on MM.1S cells. First, 17c was combined with the CRBN ligand pomalidomide, which resulted in elevated HDAC6 levels compared to 17c treatment alone. This effect arises from the competitive binding of 17c and pomalidomide to the CRBN IMiD binding site, resulting in reduced binding of 17c to this site. Next, the neddylation inhibitor MLN4924 was added to prevent neddylation-dependent proteasomal degradation. The addition of MLN4924 showed a strong rescue of HDAC6 levels indicating that 17c acts via the UPS. Tubastatin A, a selective class IIb HDAC inhibitor, was also added and prevented 17c from binding to HDAC6, thereby inhibiting ternary complex formation. HDAC6 levels were again rescued by the addition of tubastatin A.