To determine whether the degradation resulted in antiproliferative activity, viability assays were conducted (Table ). The two hematological cancer cell lines MM.1S and MV4-11 exhibited similar results: The antiproliferative activity increased from 1a to 1j, whereas the nondegrading control showed no or only minimal toxicity. The antiproliferative effects against MV4-11 cells was for all compounds more pronounced than against MM.1S. In contrast, the results in the solid tumor cell lines were notably weaker, particularly in U-87MG cells, and the potency ranking of the PROTACs changed. Importantly, the non-degrading control 1g-nc again showed no effects, reinforcing the assumption that the observed antiproliferative effects were related to ternary complex formation and subsequent HDAC degradation. When compared to the included controls, all FEM1B-recruiting PROTACs were significantly more effective than the CRBN-based A6. Notably, 1j even outperformed the clinical candidate ricolinostat in the hematological cell lines MM.1S and MV4-11, demonstrating its superior activity in these models. Clonogenic growth assay. The results of short-term cell viability assays were complemented by a clonogenic growth assay, which was used to assess the long-term effects on replicative potential of MDA-MB-231 cells. The clonogenic growth was determined by counting the number of colonies after 48 h of treatment with the respective compounds or vehicle, followed by nine days of growth. All three PROTACs (1a, 1g, 1j) showed reduced clonogenic growth, similar to the effects observed with the HDACi vorinostat and ricolinostat (Figure ). In contrast, the CRBNrecruiting degrader A6 showed no reduction in clonogenic growth. While FEM1B-recruiting PROTACs initially appeared less effective than HDAC inhibitors in short-term metabolic activity assays (Table ), their long-term efficacy was demonstrated through a significant reduction in clonogenic growth. In good agreement with the previous assays, the non-degrading control 1g-nc exhibited no significant anti-cancer effects in the clonogenic growth assay.