In this work, we utilized the Ugi four component reaction (U-4CR)-derived DCAF11 ligand of Zhang et al. to modify our previously published HDAC6 degrader A6 (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 are structurally similar to A6, 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 long-term antiproliferative activity.