The subsequent hydrazine monohydrate-mediated deprotection released the resin-bound hydroxylamine, enabling its coupling with Fmoc-7-aminoheptanoic acid which was facilitated by HATU and HOBt. This step formed the zinc-binding group and linker of the resin-bound HDAC inhibitor 3. After Fmoc-deprotection of the precursor, Fmoc-4-aminobenzoic acid was used to complete the HDACi 4. The last step before the introduction of the DCAF11 ligand was the attachment of various spacers, which was performed in the same manner as previous couplings steps to produce 5a-j. The precursors 4 and 5a-j were then used to install the DCAF11 ligand by an on resin U-4CR. To this end, 3,4-dichlorobenzaldehyde, 2-chloroacetic acid, and benzyl isocyanide were used in the U-4CR. This synthetic approach enabled the introduction of the DCAF11 ligand in one final step. Finally, all compounds were cleaved from the resin and purified by preparative HPLC to >95% purity. .02 and 4.9 (log2) transcription per million). We first examined the effects on HDAC1 and 6 protein levels, as they represent members of the most studied HDAC classes (I and IIb) and are mainly located in opposite cellular compartments (nucleus and cytoplasm).