Based on our previously published HDAC6 degrader A6, we started to design DCAF11-recruiting PROTACs (Figure ). In our previous studies, we developed a highly modular approach for the solid-phase synthesis of PROTACs and extended this approach to the synthesis of hydrophobically tagged HDAC inhibitors. Adapting the U-4CR to the solid-phase conditions allowed us to synthesize a set of eleven PROTACs entirely on resin. The subsequent biological evaluation revealed significant degradation of HDAC1, correlating with cytotoxic effects in the multiple myeloma cell line MM.1S. Notably, further investigation of compounds 1j and 2, which share the POI ligand with A6 but differ in linker length and the E3 ligase ligand, revealed enhanced degradation capabilities and both compounds induced pan-HDAC degradation across all isoforms tested. This effect was accompanied by increased cell cycle arrest, apoptosis induction, and longterm antiproliferative activity.