To assess the HDAC-degrading capabilities of 17a-d and 18a-d, we treated multiple myeloma cells (MM.1S) with our test compounds with concentration of 0.5 µM and 5 µM. Compound A6, a selective HDAC6 degrader identified in our previous study, was included as a control. 17 MM1.S cells were treated for 24 hours before HDAC6 levels were determined by immunoblot analysis, as depicted in Table and Figure (Supporting Information). Interestingly, significant HDAC6 degradation was shown by all of the CRBN-engaging compounds 17a-d, but no degradation of HDAC6 was exhibited by VHL-based compounds 18a-d. The most potent degradation of 91% was achieved by 17c at 0.5 µM. Additionally, 17a-c showed increased levels of HDAC6 at 5 µM compared to the levels at 0.5 µM. This effect was not observed for 17d. Here, at 5 µM the HDAC6 degradation was higher (90%) than at 0.5 µM (85%). It was also investigated whether HDAC1-3 could be degraded by the compounds. As shown in Figure , no degradation of HDAC1-3 was observed for any compound. [a] mean ± SD, results from at least three individual experiments.