RSL3, also known as (1S,3R)-RSL3, acts as an inhibitor of glutathione peroxidase 4 (GPX4), which is a ferroptosis activator. It diminishes the GPX4 protein levels and prompts ferroptotic cell death in head and neck cancer cells. Additionally, RSL3 elevates the levels of p62 and Nrf2 and deactivates Keap1 in HN3-rslR cells[1]. RSL3, within concentration of 8 μM over 72 hours, significantly decreases the viability of HN3 cells. The IC50 values are 0.48 μM for HN3 cells and 5.8 μM for HN3-rslR cells, respectively. RSL3, in concentrations ranging from 0 to 8 μM over a period of 24 hours, diminishes GPX4 protein levels, augments the expression of p62 and Nrf2, and deactivates Keap1 in HN3-rslR cells[1].