EPI-743 (Vatiquinone; α-Tocotrienol quinone; PTC-743; NCT04378075) is a potent cellular oxidative stress protectant, inhibits ferroptosis in cells, which could be used for the study for mitochondrial diseases. EPI-743 is a synthetic analog of vitamin E with oral activity, targets repletion of reduced intracellular glutathione
In Vitro
Ferroptosis is a form of iron- and lipid-dependent regulated cell death associated with glutathione depletion and production of lipid peroxides by lipoxygenase enzymes. EPI-743 prevents RSL3-induced ferroptosis in PCH6 patient fibroblasts with mean EC 50 potency values of 17.3-21.8 nM. EPI-743 (37, 111, 333 nM; 24 h) exhibits prevention of BODIPY 581/591 C11 lipid oxidation. EPI-743 (0.1 nM-1 mM; 48 h) potently prevents ferroptosis induced by RSL3 (2 μM), FeC (100 μM), BSO (50 μM). EPI-743 (1 μM, 3 h) is reduced to EPI-743 hydroquinone (EPI-743-HQ) in PCH6 patient fibroblasts, and EPI-743-HQ (0.1-100 μM; 30 min) inhibits human 15-LO enzyme activity with 20% inhibition at 100 μM, and IC 50 is 4.4 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: Primary fibroblasts and B-lymphocytes Concentration: 0-1 mM Incubation Time: 48 hours Result: Inhibited RSL3-mediated ferroptotic cell death in B-lymphocytes in a dose-dependent manner. Restored viability to levels comparable with untreated cells, indicating complete rescue.
