RSL3 is a VDAC-independent ferroptosis activator with selectivity for tumor cells bearing oncogenic RAS. RSL3 is the inhibitor of the glutathione peroxidase 4, which can inhibit the cysteine/glutamate amino acid transporter system xc- that blocks GSH synthesis (IC50: 100 nM).

Ferroptosis-inducing compounds inactivate GPX4 by direct binding or by depleting glutathione.After binding to GPX4, RSL3 inactivates GPX4 to induce ROS production from lipid peroxidation. RSL3's ability to induce synthetic lethality with oncogenic RAS is rapid and quite potent. This compound inhibits the growth of BJ-TERT/LT/ST/RASV12 and DRD cells as low as 10 ng/mland started to kill sensitive cells as early as 8 hr after treatment[1][2].

Prostaglandin-endoperoxide synthase (PTGS) is the key enzyme in prostaglandin biosynthesis. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2. PTGS2 encoding cyclooxygenase-2 (COX-2) is significantly upregulated after treatment with RSL3 and erastin in mice[1].

TERT/LT/ST/RASV12 cells are seeded in 10 cm dishes and treated with 1 μM staurosporine, 10 μg/ml erastin, 20 μg/ml RSL5, and 1 μg/ml RSL3 for 16 hr. Both dying cells and live cells in each 10 cm dish are harvested and collected in the same 15 ml tubes by centrifuging cell suspension at 1000 rpm for 5 min. (Only for Reference)

1219810-16-8

C23H21ClN2O5

440.88

1S,3R-RSL3;RSL3 1S;RSL3

[1]Y Xie, et al. Cell Death and Differentiation. 2016, 23:369-379. [2]Yang WS, et al. Chem Biol. 2008, 15(3):234-245. [3]Li H, Shi W, Li X, et al. Ferroptosis is Accompanied by? OH Generation and Cytoplasmic Viscosity Increase Revealed via Dual-Functional Fluorescence Probe[J]. Journal of the American Chemical Society. 2019.

[1]Wang F, Liu Y, Ni F, et al. BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency. Nature Communications. 2022, 13(1): 1-17. [2]Li H, Shi W, Li X, et al. Ferroptosis is Accompanied by? OH Generation and Cytoplasmic Viscosity Increase Revealed via Dual-Functional Fluorescence Probe. Journal of the American Chemical Society. 2019 [3]Li W, Luo L X, Zhou Q Q, et al. Phospholipid peroxidation inhibits autophagy via stimulating the delipidation of oxidized LC3-PE. Redox Biology. 2022: 102421. [4]Li P, Lin Q, Sun S, et al. Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism. Cell Death & Disease. 2022, 13(9): 1-15. [5]Fang Y, Tan Q, Zhou H, et al. Discovery and optimization of 2-(trifluoromethyl) benzimidazole derivatives as novel ferroptosis inducers in vitro and in vivo. European Journal of Medicinal Chemistry. 2022: 114905. [6]Ning X, Qi H, Yuan Y, et al. Identification of a new small molecule that initiates ferroptosis in cancer cells by inhibiting the system Xc? to deplete GSH. European Journal of Pharmacology. 2022: 175304. [7]Peng X, Tan Q, Wu L, et al. Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3, 4-Epoxy Group-Containing Abietanes. Journal of Natural Products. 2022 [8]Zhang H, Shan G, Jin X, et al. ARNTL2 is an indicator of poor prognosis, promotes epithelial-to-mesenchymal transition and inhibits ferroptosis in lung adenocarcinoma. Translational Oncology. 2022, 26: 101562. [9]Peng, Xing, et al. Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors. Fitoterapia. (2021): 104984.

DMSO:44.1 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years