(see Scheme S1A for synthetic details, Supplementary Information). As a first step, the degradation ability of AP7 and AP8 on HDAC6 and HDAC10 was evaluated. Interestingly, both degraders exhibited comparable HDAC6 and 10 degradation potencies to AP1 at 1 μM in MM.1S cells. Of note, a "hook effect" in HDAC6 degradation was observed for AP8 at 5 μM (Figure ). Next, we evaluated the degradation selectivity of AP7 and AP8 using HDAC8, a common off-target of HDAC6 modulators, as representative isoform. Noteworthy, both degraders with rigid linkers exhibited noticeable HDAC8 degradation, whereas the more flexible AP1 had minimal impact on HDAC8 levels (Figure ).