This technology includes the identification and use of small molecules to rescue cells undergoing ferroptosis, a type of programmed cell death. These small molecules can be used as treatments in situations where epithelial cells are being damaged, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders. Ferroptosis is a type of programmed cell death that is triggered by an increased presence of oxidants. The small molecules included in this invention target a complex between 15-Lipoxygenase-2 (15-LOX-2) and phosphatidylethanolamine binding protein 1 (PEBP1) that plays a crucial role in ferroptosis.
Further clinical work could establish the small molecules of this invention as treatments in situations where modulating the programmed cell death ferroptosis may improve clinical outcomes, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders.
There is currently a need for an impactful therapy in situations where ferroptosis causes poor clinical outcomes. The therapeutic use of antioxidants is used in some cases, such as traumatic brain injury. Clinical trials with non-specific antioxidants have failed. The small molecules included in this technology are the first targeted modulators of the ferroptosis cell death pathway.