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. Notably, 2 and 1j displayed superior antiproliferative activity in MM.1S cells compared to ricolinostat, a HDACi currently under clinical investigation. In contrast, the thalidomide-based PROTAC A6 showed no effect on the viability of MM.1S cells.