However, 1j-nc exhibited some impact on MM.1S and U-87MG, but consistently weaker compared to the PROTACs. This could be attributed to the cytotoxic effects of the HDAC inhibitor incorporated into 1j-nc. emerging as the more efficient degrader. In detail, FF2039 could achieve a pronounced degradation of all four tested isoforms (71 -90%), demonstrating robust pan-HDAC degradation activity. This demonstrates not only the successful incorporation of a DCAF11 recruiter for targeted HDAC degradation but also underscores the critical role of the chosen E3 ligase in determining degradation selectivity. Similar to the shift in degradation selectivity observed when PROTAC IV was transitioned to V by replacing IAP with VHL, we showed that substituting the CRBN ligand with a DCAF11 recruiter shifted selectivity from HDAC6-specific to pan-HDAC degradation. To verify that degradation is mediated via DCAF11 recruitment, we synthesized the nondegrading control 1j-nc based on FF2039. No effect on HDAC1 and HDAC6 levels was observed with 1j-nc, confirming the necessity of covalent binding to the E3 ligase for effective degradation.