RSL3

Catalog No.S8155 Batch:S815506

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Technical Data

Formula

C23H21ClN2O5
Molecular Weight 440.88 CAS No. 1219810-16-8
Solubility (25°C)* In vitro DMSO 88 mg/mL (199.6 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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].

Protocol (from reference)

Cell Assay:

[1]
  • 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.
Animal Study:

[1]
  • Animal Models

    athymic nude mice(8 weeks)implanted with subcutaneous xenograft tumors derived from BJeLR cells

  • Dosages

    100 mg/kg

  • Administration

    s.c. injection

References

  • https://pubmed.ncbi.nlm.nih.gov/18355723/
  • https://pubmed.ncbi.nlm.nih.gov/26794443/

Customer Product Validation

<p>(D) Representative western blot and (E) densitometry showing protein levels of HO-1 in HO-1+/+ PTCs treated with RSL3 over time. Data shown represent the Mean ± SEM of three independent experiments performed each time in triplicate; * = p<0.05, ** = p<0.01 compared to lower concentration at each time point.</p>

, , Am J Physiol Renal Physiol, 2017, doi: 10.1152/ajprenal.00044.2017

Fluvastatin treatment of HT-1080 cells decreases GPX4 protein levels in a time- and concentration-dependent manner and synergized with co-treatment with the direct GPX4 inhibitor RSL3.

Data from [ , , Nature, 2017, 547(7664):453-457 ]

HK2 cells with elevated PEBP1 are more sensitive to ferroptosis. Inset: ferrostatin-1-inhibitable cell death (means ± SD, *p < 0.05 versus pCMV6, **p < 0.05 versus pCMV6/RSL3, ***p < 0.05 versus pCMV6-PEBP1/RSL3, #p < 0.05 versus pCMV6/RSL3, n = 3/group). Inset: quantitation of ferroptosis as differences in LDH in ± FER-treated cells.

Data from [ , , Cell, 2017, 171(3):628-641 ]

ATG3 is required for ferroptosis. ATG3KO MEFs, or ATG3KO cells reconstituted with ectopic ATG3 expression, were treated as indicated for 12 h. Cell death was determined by PI staining coupled with flow cytometry. ATG3 expression was confirmed by immunoblotting. erastin: 1 μM; RSL3: 1 μM.

Data from [ , , Cell Res, 2016, 26(9):1021-32 ]

Selleck's RSL3 Has Been Cited by 509 Publications

The Role of Compartmentalized Metabolism in Cellular Metal Homeostasis [ Rockefeller University Digital Commons @ RU, 221, 670] PubMed: None
ANXA1 inhibits ferroptosis in HUVECs via negative regulation of ferritinophagy [ Exp Cell Res, 2026, 454(1):114825] PubMed: 41241173
NINJ1 regulates plasma membrane fragility under mechanical strain [ Nature, 2025, 10.1038/s41586-025-09222-5] PubMed: 40490006
Multiple oestradiol functions inhibit ferroptosis and acute kidney injury [ Nature, 2025, 10.1038/s41586-025-09389-x] PubMed: 40804518
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia [ Cell, 2025, S0092-8674(25)01233-4] PubMed: 41265435
Endoplasmic reticulum-mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis [ Nat Cell Biol, 2025, 27(6):902-917] PubMed: 40514428
Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity [ Nat Metab, 2025, 7(2):297-320] PubMed: 39815080
BDH2-driven lysosome-to-mitochondria iron transfer shapes ferroptosis vulnerability of the melanoma cell states [ Nat Metab, 2025, 7(9):1851-1870] PubMed: 40957995
Single-atom Pt-doped ceria nanozymes mitigate myocardial ischemia reperfusion injury via cardiomyocyte-targeted uptake and suppression of reactive oxygen species [ Bioact Mater, 2025, 53:366-385] PubMed: 40727484
Regulation of enzymatic lipid peroxidation in osteoblasts protects against postmenopausal osteoporosis [ Nat Commun, 2025, 16(1):758] PubMed: 39824794

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.