RSL-3

An oncogenic RAS-selective lethal compound that actvates iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells, inhibits glutathione peroxidase (GPX4) and induces ferroptosis in BJeLR cells (EC50=10 nM) ; increases PTGS2 expression and significantly inhibits tumor growth in a xenograft mouse model (100 mg/kg) . (In Vitro) :RSL3 (0-8 μM, 72 hours) potently reduces the viability of HN3 cells, with IC50s of 0.48 μM in HN3 and 5.8 μM in HN3-rslR cells, respectively.RSL3 (0-8 μM, 24 hours) reduces the expression of GPX4 protein, increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells. (In Vivo) :RSL3 (100 mg/kg, Intratumorally twice per week for 20 days) significantly inhibits the growth of tumor in combination with trigonelline in mice bearing HN3R cells.