AY-4 (Compound AY-4) is a potent PROTAC degrader targeting FTH1, with a dissociation constant (Kd) of 3.17 nM. It effectively increases intracellular ferrous (Fe2+) and ferric (Fe3+) ion levels. AY-4 is a potential anticancer candidate that regulates iron homeostasis through ferritin degradation, enhancing the efficacy of existing drugs. Additionally, AY-4 significantly reduces FTH1 levels in breast cancer cells.

AY-4 (Compound AY-4) is effective in enhancing the efficacy of Artesunate and Palbociclib in MCF-7 cells by releasing iron ions at a concentration of 50 μM over 24-48 hours. Additionally, AY-4 acts as an efficient FTH1 degrader in both MCF-7 and T47D cells at 50 μM for 12 hours. The L-configuration ligand of AY-4, ranging from 0.005 to 50 μM for 12 hours, is essential for FTH1 degradation activity. Furthermore, AY-4 at 50 μM can increase intracellular ferrous ion (Fe2+) levels without causing significant oxidative stress.