These findings correlate well with the observed degradation of HDAC1 and 6. While 1a and 1b had no effect on HDAC1 and 6 levels, 2 and 1j demonstrated significant degradation of both HDAC1 and 6. In addition, 2 and 1j displayed superior antiproliferative activity in MM.1S cells compared to ricolinostat, an HDACi currently under clinical investigation. Furthermore, we investigated the contribution of the DCAF11 ligand to the antiproliferative activity of the PROTACs. To this end, we synthesized the n-propyl-substituted DCAF11 warhead 6 (see Scheme S1, Supporting Information) and tested a 1:1 combination of vorinostat and 6 in a cell viability assay. Since the EC50 of the combination treatment was similar to that of vorinostat alone, the DCAF11 ligand seems not to add significant cytotoxicity (Figure , Supporting Information). In contrast, the thalidomide-based PROTAC A6 showed no effect on the viability of MM.1S cells, consistent with the previous reports showing little to no effects of A6 depending on the cell line. Notably, the antiproliferative activity of 2 and 1j is reduced by a factor of ~ 3 -6 compared to the parent HDACi vorinostat, which is comparable to the previously published FEM1B-recruiting