Design and synthesis of DCAF11-recruiting HDAC PROTACs. The design of our PROTACs was based on the best degrader of our previous HDAC degrader study, A6, which combines a vorinostat-like HDAC inhibitor and a thalidomide-based CRBN ligand, fused by a C7 aliphatic spacer (Figure ). Although vorinostat is a pan-HDAC inhibitor, A6 specifically targeted HDAC6 for degradation. The aim of this study was to investigate how switching the E3 ligase affects the HDAC degradation selectivity profile.