RSL3

Synonyms: (1S,3R)-RSL3

RSL3 ((1S,3R)-RSL3) is a ferroptosis activator in a VDAC-independent manner,exhibiting selectivity for tumor cells bearing oncogenic RAS. RSL3 binds, inactivates GPX4 and thus mediates GPX4-regulated ferroptosis.

RSL3 Chemical Structure

RSL3 Chemical Structure

CAS: 1219810-16-8

Selleck's RSL3 has been cited by 316 publications

Purity & Quality Control

Batch: Purity: 99.97%
99.97

Products often used together with RSL3

Erastin


RSL3 and Erastin are ferroptosis inducers (FINs) and sensitize cancer cells (H460/A549) to ionizing radiation (IR).


Lei G, et al. Cell Res. 2020;30(2):146-162.

Fer-1 (Ferrostatin-1)


Ferrostatin-1 (Fer-1) efficiently abrogates the rise in reactive oxygen species (ROS) levels caused by RSL3 in M0/M1/M2 macrophages.


Chen W, et al. Front Cell Dev Biol. 2021 Dec 31;9:791187.

Liproxstatin-1


RSL3-induced lipid oxidation is prevented by Liproxstatin-1 in human renal proximal tubular epithelial cells (HRPTEpiCs).


Friedmann Angeli JP, et al. Nat Cell Biol. 2014;16(12):1180-1191.

FIN56


RSL3 and FIN56 are ferroptosis inducers that cause a decrease in GPX4 protein abundance in HT-1080 cells.


Gaschler MM, et al. Nat Chem Biol. 2018;14(5):507-515.

ML 210


RSL3 and ML 210 induce lipid reactive oxygen species (ROS) and iron-dependent cell death in small-cell lung cancer (SCLC).


Bebber CM, et al. Nat Commun. 2021 Apr 6;12(1):2048.

RSL3 Related Products

Choose Selective Ferroptosis Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MEFs and HT1080 cells Function assay 0.5 μM 24 h 30686534
Jurkat Cell death assay 0.1 μM 24 h or 48 h BV6 cooperates with RSL3 to induce cell death, accompanied by ROS production and lipid peroxidation 27588473
Molt-4 Cell death assay 0.075 μM 24 h or 48 h BV6 cooperates with RSL3 to induce cell death, accompanied by ROS production and lipid peroxidation 27588473
RMS13 cells Cell death assay 0, 60, 100, 140 and 180 μM 48 h Addition of Ferrostatin-1 significantly reduced RSL3- or Erastin-induced loss of cell viability. 26157704
BJeLR Cytotoxicity assay 0.57 uM 12 h Cytotoxicity against human BJeLR cells expressing RAS G12V mutant at 0.57 uM at 12 hrs by trypan blue staining 22832321
BJeLR Cytotoxicity assay 0.57 uM 24 h Cytotoxicity against human BJeLR cells expressing RAS G12V mutant at 0.57 uM at 24 hrs by trypan blue staining 22832321
BJeH Function assay 6 h Induction of reactive oxygen species production in human BJeH cells expressing wild type RAS after 6 hrs by DCF-based flow cytometric analysis 22832321
BJeLR Function assay 6 h Induction of reactive oxygen species production in human BJeLR cells expressing RAS G12V mutant after 6 hrs by DCF-based flow cytometric analysis 22832321
Click to View More Cell Line Experimental Data

Biological Activity

Description RSL3 ((1S,3R)-RSL3) is a ferroptosis activator in a VDAC-independent manner,exhibiting selectivity for tumor cells bearing oncogenic RAS. RSL3 binds, inactivates GPX4 and thus mediates GPX4-regulated ferroptosis.
Targets
Gpx4 [1]
(In Calu-1 cells)
In vitro
In vitro 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].
Cell Research Cell lines TERT/LT/ST/RASV12 cells 
Concentrations 1 µg/ml
Incubation Time 16hrs
Method

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.

Experimental Result Images Methods Biomarkers Images PMID
Western blot GPX4 / Tranferrin / Ferritin HO-1 30524291
Growth inhibition assay Cell viability 26157704
Immunofluorescence ALOX12 / ALOX15 4-HNE 28837253
In Vivo
In vivo 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].
Animal Research Animal Models athymic nude mice(8 weeks)implanted with subcutaneous xenograft tumors derived from BJeLR cells
Dosages 100 mg/kg
Administration s.c. injection

Chemical Information & Solubility

Molecular Weight 440.88 Formula

C23H21ClN2O5

CAS No. 1219810-16-8 SDF Download RSL3 SDF
Smiles COC(=O)C1CC2=C(C(N1C(=O)CCl)C3=CC=C(C=C3)C(=O)OC)NC4=CC=CC=C24
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 88 mg/mL ( (199.6 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 28 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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