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RSL3

Catalog No. T3646   CAS 1219810-16-8
Synonyms: RSL3 1S, 1S,3R-RSL3

RSL3 (RSL3 1S) is an inhibitor of GPX4, and inhibits system xc- that blocks GSH synthesis (IC50=100 nM). RSL3 is a VDAC-independent activator of iron death that is selective for tumor cells carrying oncogenic RAS.

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RSL3 Chemical Structure
RSL3, CAS 1219810-16-8
Pack Size Availability Price/USD Quantity
1 mg In stock $ 33.00
2 mg In stock $ 47.00
5 mg In stock $ 72.00
10 mg In stock $ 128.00
25 mg In stock $ 271.00
50 mg In stock $ 368.00
100 mg In stock $ 483.00
500 mg In stock $ 1,080.00
1 g In stock $ 1,430.00
1 mL * 10 mM (in DMSO) In stock $ 68.00
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Purity: 99.96%
Purity: 99.64%
Purity: 99.39%
Purity: 99.23%
Purity: 98.06%
Purity: 98%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description RSL3 (RSL3 1S) is an inhibitor of GPX4, and inhibits system xc- that blocks GSH synthesis (IC50=100 nM). RSL3 is a VDAC-independent activator of iron death that is selective for tumor cells carrying oncogenic RAS.
Targets&IC50 GSH:100 nM
In vitro METHODS: Human hepatocellular carcinoma cells HepG2, HA22T/VGH were treated with RSL3 (0.1-10 μM) for 72 h, and cell growth inhibition was detected by MTT.
RESULTS: RSL3 dose-dependently inhibited the growth of HepG2 and HA22T/VGH cells, with an IC50 of about 0.07 μM for HepG2 cells and 0.3 μM for HA22T/VGH cells. [1]
METHODS: Human glioblastoma cells U87 and U251 were treated with RSL3 (0.25 μM and 0.5 μM) for 24 h, and the expression levels of target proteins were detected by Western Blot.
RESULTS: RSL3 treatment induced a decrease in the expression of iron death-related proteins GPX4, ATF4 and xCT, and an up-regulation in the expression of HO-1 in U87 and U251 cells. [2]
METHODS: Human colorectal cancer cells HCT116 and LoVo were treated with RSL3 (3 μM) for 24 h. Labile iron pool (LIP) and ROS intracellular levels were analyzed by Flow Cytometry.
RESULTS: RSL3 promoted the increase of LIP and accumulation of ROS associated with iron death. [3]
In vivo METHODS: To test the antitumor activity in vivo, RSL3 (100 mg/kg in 20 μL DMSO plus 80 μL corn oil) was intraperitoneally injected into NSG mice bearing human prostate cancer tumors DU145 or PC3 twice a week for sixteen days.
RESULTS: RSL3 treatment significantly inhibited the growth of human prostate cancer tumors, indicating antitumor activity in vivo. [4]
METHODS: To detect anti-tumor activity in vivo, RSL3 (1 mg/kg) and cetuximab (13 mg/kg) were intraperitoneally injected once a week for sixteen days into BALB/c nude mice harboring KRAS-mutant human colorectal cancer tumor DLD-1.
RESULTS: RSL3 treatment significantly inhibited the growth of KRAS-mutant tumors. Cetuximab enhanced RSL3-induced iron death by activating p38 MAPK and inhibiting the Nrf2/HO-1 axis, which further inhibited tumor growth. [5]
Cell Research 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)
Synonyms RSL3 1S, 1S,3R-RSL3
Molecular Weight 440.88
Formula C23H21ClN2O5
CAS No. 1219810-16-8

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 44.1 mg/mL (100 mM)

TargetMolReferences and Literature

1. Asperti M, et al. H-ferritin suppression and pronounced mitochondrial respiration make Hepatocellular Carcinoma cells sensitive to RSL3-induced ferroptosis. Free Radic Biol Med. 2021 Jun;169:294-303. 2. Li S, et al. RSL3 Drives Ferroptosis through NF-κB Pathway Activation and GPX4 Depletion in Glioblastoma. Oxid Med Cell Longev. 2021 Dec 26;2021:2915019. 3. Sui X, et al. RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer. Front Pharmacol. 2018 Nov 22;9:1371. 4. Ghoochani A, et al. Ferroptosis Inducers Are a Novel Therapeutic Approach for Advanced Prostate Cancer. Cancer Res. 2021 Mar 15;81(6):1583-1594. 5. Yang J, et al. Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer. Cell Death Dis. 2021 Nov 13;12(11):1079.

TargetMolCitations

1. Hu G, Cui Z, Chen X, et al.Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism‐Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu.Advanced Science.2023: 2206439. 2. Feng Y, Luo X, Li Z, et al.A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy.Nature Communications.2023, 14(1): 5083. 3. Bi G, Liang J, Shan G, et al.Retinol saturase mediates retinoid metabolism to impair a ferroptosis defense system in cancer cells.Cancer Research.2023: CAN-22-3977. 4. Li Y, Yang W, Zheng Y, et al.Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis.Journal of Experimental & Clinical Cancer Research.2023, 42(1): 1-19. 5. Wang X, Ji Y, Qi J, et al.Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.Cell Death & Disease.2023, 14(8): 1-13. 6. Tan Q, Zhang X, Li S, et al.DMT1 differentially regulates mitochondrial complex activities to reduce glutathione loss and mitigate ferroptosis.Free Radical Biology and Medicine.2023 7. Zhao G, Liang J, Shan G, et al.KLF11 regulates lung adenocarcinoma ferroptosis and chemosensitivity by suppressing GPX4.Communications Biology.2023, 6(1): 570. 8. Bow Y D, Ko C C, Chang W T, et al.A novel quinoline derivative, DFIQ, sensitizes NSCLC cells to ferroptosis by promoting oxidative stress accompanied by autophagic dysfunction and mitochondrial damage.Cancer Cell International.2023, 23(1): 1-11. 9. Gartzke L P, Hendriks K D W, Hoogstra-Berends F, et al.Inhibition of Ferroptosis Enables Safe Rewarming of HEK293 Cells following Cooling in University of Wisconsin Cold Storage Solution.International Journal of Molecular Sciences.2023, 24(13): 10939. 10. Jiang X, Teng X, Shi H, et al.Discovery and optimization of olanzapine derivatives as new ferroptosis inhibitors.Bioorganic Chemistry.2023: 106393.
11. Liu J, Meng F, Lv J, et al.Comprehensive Monitoring of Mitochondrial Viscosity Variation during Different Cell Death Processes by a NIR Mitochondria-targeting Fluorescence Probe.Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy.2023: 122602. 12. Li Y, Bao Y, Li Y, et al.RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis.Viruses.2023, 15(10): 2080. 13. Shi H, Jiang X, Cao L, et al.Chemical constituents of Ajuga forrestii and their anti-ferroptosis activity.Fitoterapia.2023: 105461. 14. 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. 15. Peng, Xing, et al. Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors. Fitoterapia. (2021): 104984. 16. 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. 17. 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 18. 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. 19. 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. 20. 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. 21. 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. 22. 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 23. Shan G, Bi G, Zhao G, et al.Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer.Respiratory Research.2023, 24(1): 1-15. 24. Cao Z, Liu X, Zhang W, et al.Biomimetic Macrophage Membrane-Camouflaged Nanoparticles Induce Ferroptosis by Promoting Mitochondrial Damage in Glioblastoma.ACS nano.2023 25. Teng X, Shi H, Cao L, et al.Chemical Constituents of Ajuga lupulina and Their Anti‐ferroptosis ActivityChemical Constituents of Ajuga lupulina and Their Anti‐ferroptosis Activity.Chemistry & Biodiversity.2024: e202400244. 26. Xu L, Wen B, Wu Q, et al.Long non-coding RNA KB-1460A1. 5 promotes ferroptosis by inhibiting mTOR/SREBP-1/SCD1-mediated polyunsaturated fatty acid desaturation in glioma.Carcinogenesis.2024: bgae016.
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Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Active Compound Library Oxidation-Reduction Compound Library Antioxidant Compound Library Bioactive Compound Library Target-Focused Phenotypic Screening Library Apoptosis Compound Library Metabolism Compound Library Inhibitor Library Covalent Inhibitor Library Cysteine Covalent Library

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Keywords

RSL3 1219810-16-8 Apoptosis Metabolism oxidation-reduction Ferroptosis GPX Glutathione Peroxidase inhibit RSL-3 (1S,3R)-RSL3 RSL3 1S 1S,3R-RSL3 Inhibitor RSL 3 inhibitor

 

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