RSL3

RSL3 ((1S,3R) -RSL3) is an inhibitor of glutathione peroxidase 4 (GPX4) (ferroptosis activator), reduces the expression of GPX4 protein, and induces ferroptotic death of head and neck cancer cell. RSL3 increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells[1].

Product Specifications

CAS Number

[1219810-16-8]

Product Name Alternative

(1S,3R) -RSL3

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

Ferroptosis; Glutathione Peroxidase; p62; Reactive Oxygen Species (ROS)

Type

Reference compound

Related Pathways

Apoptosis; Autophagy; Immunology/Inflammation; Metabolic Enzyme/Protease; NF-κB

Applications

Cancer-programmed cell death

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/RSL3-1S,3R-.html

Purity

99.87

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

O=C([C@H]1CC2=C([C@H](C3=CC=C(C(OC)=O)C=C3)N1C(CCl)=O)NC4=C2C=CC=C4)OC

Molecular Formula

C23H21ClN2O5

Molecular Weight

440.88

Precautions

H302, H315, H319, H335

References & Citations

[1]Shin D, et al. Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic Biol Med. 2018 Dec;129:454-462.|[2]Romani P, et al., Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance. Nat Cell Biol. 2022 Feb;24 (2) :168-180.|[3]Zhang Z, et al., CGI1746 targets σ1R to modulate ferroptosis through mitochondria-associated membranes. Nat Chem Biol. 2024 Jan 11. |[4]Chen T, et al., Mitochondrial transplantation rescues neuronal cells from ferroptosis. Free Radic Biol Med. 2023 Nov 1;208:62-72. |[5]Zhu JF, et al., Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway. Cell Death Dis. 2023 Feb 23;14 (2) :151. |[6]Song H, et al., A potent GPX4 degrader to induce ferroptosis in HT1080 cells. Eur J Med Chem. 2024 Feb 5;265:116110.|[7]Zheng J, et al., Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines. Cell Death Dis. 2021 Jul 13;12 (7) :698. |[8]Cheff DM, et al., The ferroptosis inducing compounds RSL3 and ML162 are not direct inhibitors of GPX4 but of TXNRD1. Redox Biol. 2023 Jun;62:102703. |[9]Li P, et al., Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism. Cell Death Dis. 2022 Sep 21;13 (9) :808.|[10]Brown CW, et al., Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export. Dev Cell. 2019 Dec 2;51 (5) :575-586.e4.