Having confirmed FerroTACs` degradation activity, we investigated the potential for undesired intrinsic cytotoxicity of ferrocene since ferrocene is commonly used in antitumoral and antiparasitic therapies due to its ability to mediate reactive oxygen species (ROS) production through the Fenton reaction. Therefore, we assessed the impact of the BETdegrading FerroTAC AS6 on the viability of BET-sensitive HCT116 cells and HEK293 cells (Figure ). The best performing BET-degrading PROTAC AS6 was chosen for cytotoxicity investigation due to the reliability of BET-sensitive cell lines (HCT116), which help differentiate between unspecific cytotoxic effects from those arising from on-target degradation. In HCT116, AS6 exhibited a significant antiproliferative effect, with IC50 = 10.1 µM only tenfold lower than MZ1 (IC50 = 1.33 µM), and consistent with its less pronounced degradation profile. Importantly, AS6, similarly to MZ1, showed almost no intrinsic cytotoxicity in HEK293 cells (Figure ) highlighting the inherent tolerability and non-toxicity of ferrocene itself. These findings further support that degradation is the primary mechanism driving cytotoxicity in BET-sensitive cell lines, while ferrocene is well tolerated in a cellular context up to high micromolar concentrations.