RSL3 Ferroptosis inducer

Cat.No.S8155

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 Ferroptosis activator Chemical Structure

Chemical Structure

Molecular Weight: 440.88

Quality Control

Products Often Used Together with RSL3

Erastin

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

Ferrostatin-1 (Fer-1)

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

Liproxstatin-1

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

FIN56

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

ML 210

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

Cell Culture, Treatment & Working Concentration

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

Chemical Information, Storage & Stability

Molecular Weight 440.88 Formula

C23H21ClN2O5

Storage (From the date of receipt)
CAS No. 1219810-16-8 Download SDF Storage of Stock Solutions

Synonyms (1S,3R)-RSL3 Smiles COC(=O)C1CC2=C(C(N1C(=O)CCl)C3=CC=C(C=C3)C(=O)OC)NC4=CC=CC=C24

Solubility

In vitro
Batch:

DMSO : 88 mg/mL (199.6 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 28 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Mechanism of Action

Targets/IC50/Ki
Gpx4 [1]
(In Calu-1 cells)
In vitro
Ferroptosis-inducing compounds inactivate GPX4 by direct binding or by depleting glutathione.After binding to GPX4, this compound inactivates GPX4 to induce ROS production from lipid peroxidation. Its 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].
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 this compound in mice[1].
References

Applications

Methods Biomarkers Images PMID
Western blot GPX4 / Tranferrin / Ferritin HO-1 S8155-WB2 30524291
Growth inhibition assay Cell viability S8155-viability1 26157704
Immunofluorescence ALOX12 / ALOX15 4-HNE S8155-IF2 28837253

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