Following the target engagement and human plasma stability assays, we evaluated the degradation efficacy of compounds AP1-AP6. Western blot analyses of HDAC6 and HDAC10 protein levels were respectively. Conversely, compound AP2 showed approximately 20% degradation of both targets at 5 μM, while achieving 68% degradation of HDAC6 at 1 μM. However, no degradation of HDAC10 was observed at this concentration. Compound AP5 demonstrated only slight degradation of both targets at 5 μM, with negligible effects observed at 1 μM. The relatively diminished degradation potencies of compounds AP2 and AP5, when compared with AP1, AP3, AP4, and AP6, may be attributed to their longer linkers, potentially affecting the formation of a productive ternary complex.