RSL3 (Synonyms: (1S,3R)-RSL3)

Name: RSL3
Brand: MedChemExpress
SKU: HY-100218A
Rating: 5.0 (262 reviews)

Cat. No.: HY-100218A Purity: 99.90%: FAQs
Data Sheet SDS COA Handling Instructions

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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.

For research use only. We do not sell to patients.

RSL3 Chemical Structure

CAS No. : 1219810-16-8

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 87	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 87	In-stock	Estimated Time of Arrival: December 31
Solid
2 mg	USD 60	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 90	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 160	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 330	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 560	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 990	In-stock	Estimated Time of Arrival: December 31
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500 mg		Get quote

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Based on 262 publication(s) in Google Scholar

Other Forms of RSL3:

RSL3 Get quote
(1R,3S)-RSL3 Get quote
(1R,3R)-RSL3 Get quote

MedChemExpress Activity Verification

Above results were obtained through MCE biological verification.

248 Publications Citing Use of MCE RSL3

Proliferation Assay

IHC

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Discov. 2022 May 3;8(1):40. [Abstract]; U2OS cells are treated with OSMI-1 (30 μM) or TMG (10 μM) for 12 h, and then induced with or without RSL3 (10 μM) for 6 h.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Discov. 2022 May 3;8(1):40. [Abstract]; U2OS cells are treated with DMSO (Control) or OSMI-1 for 12 h, and then treated with RSL3 (10 μM) for different time as indicated. The levels of cellular ferrous iron are assessed by flow cytometry using FerroOrange.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Discov. 2022 May 3;8(1):40. [Abstract]; U2OS cells are treated with DMSO (Control) or OSMI-1 for 12 h, and then treated with RSL3 (10 μM) for different time as indicated. Cells are then subjected to immunofluorescence microscopy with antibodies against TfR1 and GM130.

: RSL3 purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2022 Apr;3(4):471-485. [Abstract]; Cellular responses of neuroblastoma cell lines to 72 h of RSL3 treatment: cells with MYCN amplification (black symbols), moderate MYCN expression (white circle) and lack thereof (white triangle).

: RSL3 purchased from MedChemExpress. Usage Cited in: Redox Biol. 2022 Jul 31;55:102408. [Abstract]; Immune blot detection of FSP1, GCLC, GCLM, and GPX4 in total protein extracts from the cell lines exposed to RSL3 or L-BSO for 24 h. The concentrations used are 0.25 and 1 μM RSL3 for CTV-1, Jurkat, K562 and HCT-116. For MOLT-16 RSL3 is used at 0.05 and 0.25 μM.

: RSL3 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2022 Jun 21;18(10):4135-4150. [Abstract]; CCK-8 assay assessed the cell viability of PANC1 and PaTU8988 cells treated DMSO, Erastin (4, 15 µM) and RSL3 (0.5, 5 µM) with or without SC-26196 (10 µM).

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 May 30;13(5):507. [Abstract]; HE staining of retinal tissue in mice that underwent sham or IR injury at 3 and 7 d after intravitreal injection of vehicle (DMSO) or 50 μM Erastin and 500 nM RSL-3.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 Sep 26;13(9):825. [Abstract]; MSCs are treated with Erastin (100 nmol/L) or RSL3 (10 nmol/L) or treated with Fer-1 (10 μmol/L) or Lip-1 (20 μmol/L) during SPIO labeling. Cells are harvested at 24 h.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 Sep 26;13(9):825. [Abstract]; MSCs are treated with Erastin (100 nmol/L) or RSL3 (10 nmol/L) or treated with Fer-1 (10 μmol/L) or Lip-1 (20 μmol/L) during SPIO labeling. Cells are harvested at 24 h. A Cell viability of MSCs under different treatment was measured by CCK-8 assay. Both of them reduce the cell viability of MSCs and induce the level of ROS and lipid peroxide in MSCs.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2022 Jul 20;13(7):630. [Abstract]; ROS levels are detected in pancreatic cancer cells from different treatment groups with a ROS Assay Kit. MDA and GSH-PX levels are detected in RSL3 (3 μM; 24 h) of treated Panc-1, MIA PaCa-2, and BxPC-3 cells.

: RSL3 purchased from MedChemExpress. Usage Cited in: Redox Biol. 2021 Nov;47:102174. [Abstract]; HT1080 fibrosarcoma cells are exposed to RSL3 (10 μM, 24 h), and phorbol myristate acetate (PMA)-primed THP1 macrophage cells were exposed to crocidolite in the presence of absence of ferric ammonium citrate (Fe, 100 μg/ml) up to 96 h. Membrane-catch transmission electronmicroscopy (TEM) images of EVs on carbon grids.

: RSL3 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2021 Nov 13;12(11):1079. [Abstract]; The protein levels of Keap1, Nrf2 and HO-1 in HCT116 and DLD-1 cells are measured by western blotting after treatment with RSL3 (1 μM), cetuximab (100 μg/ml) or their combination for 24 h.

: RSL3 purchased from MedChemExpress. Usage Cited in: Brain Res Bull. 2020 Oct;163:40-48. [Abstract]; Gpx4 and 4-HNE expression assessment by Western blotting after RSL3 treatment. Western blot analysis reveal that compared with the Mel group, the RSL3 group has significantly decreased and increased Gpx4 and 4-HNE expression, respectively.

: RSL3 purchased from MedChemExpress. Usage Cited in: Brain Res Bull. 2020 Oct;163:40-48. [Abstract]; Representative images and NeuN + cell quantification in the hippocampus via immunohistochemistry after RSL3 treatment. Compared with the Mel group, the RSL3 group has a significantly decreased NueN + cell number.

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Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

Glutathione peroxidase 4^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
4T1	IC₅₀	3.69 μM Compound: RSL3	Cytotoxicity against human 4T1 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human 4T1 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34506134]
HT-1080	IC₅₀	1.2 μM Compound: RSL3	Cytotoxicity against human HT-1080 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human HT-1080 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34506134]
HT-1080	IC₅₀	3.7 μM Compound: RSL3	Cytotoxicity against human HT-1080 cells assessed as reduction in cell viability incubated for 48 hrs in presence of Fer-1 by MTT assay Cytotoxicity against human HT-1080 cells assessed as reduction in cell viability incubated for 48 hrs in presence of Fer-1 by MTT assay	[PMID: 34506134]
MCF7	IC₅₀	13.57 μM Compound: RSL3	Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34506134]

In Vitro

RSL3 (0-8 μM, 72 hours) potently reduces the viability of HN3 cells, with IC₅₀s of 0.48 μM in HN3 and 5.8 μM in HN3-rslR cells, respectively^[1].
RSL3 (0-8 μM, 24 hours) reduces the expression of GPX4 protein, increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells^[1].

Ferroptosis-sensitive Cell Lines

Ferroptosis-sensitive Cells	Test Conditions
MCF10A-RAS^[2]	0-10 μM; 48 h
MDA-MB-468^[3]	0.1-1 μM; 24 h
PC-3^[3]	0.01-1 μM; 24 h
Huh-7^[3]	0.01-1 μM; 24 h
Raji^[3]	0.01-1 μM; 24 h
MEF^[3]	0.1-100 nM; 24 h
HT-22 neuron^[4]	200 nM; 16 h
NCI-H508^[5]	0.1-10 μM; 48 h
LoVo^[5]	0.1-10 μM; 48 h
LS513^[5]	0.1-10 μM; 48 h
SW480^[5]	0.1-10 μM; 48 h
SW620^[5]	0.1-10 μM; 48 h
SW1116^[5]	0.1-10 μM; 48 h
DLD-1^[5]	0.1-10 μM; 48 h
Caco-2^[5]	0.1-10 μM; 48 h
HT-1080^[6]	0-10 μM; 48 h; IC₅₀ 1.55 μM
MDA-MB-436^[7]	0.1-2 μM; 24 h
HT-29^[7]	0.1-2 μM; 24 h
U-373^[7]	0.1-2 μM; 24 h
A549^[8]	1 nM-100 μM; 24 h; IC₅₀ 0.5 μM
H1975^[8]	1 nM-100 μM; 24 h; IC₅₀ 150 nM
MAD-MB-231^[9]	0-10 μM; 96 h; IC₅₀ 0.71 μM
HCC1937^[9]	0-10 μM; 96 h; IC₅₀ 0.85 μM

Ferroptosis-insensitive Cell Lines

Ferroptosis-insensitive Cells	Test Conditions
HS578T^[10]	0-2.5 μM; 24 h
MCF10A^[10]	0-2.5 μM; 24 h

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

Cell Line:	HN3 cells, HN3-rslR cells
Concentration:	0-8 μM
Incubation Time:	72 hours
Result:	Showed IC₅₀s of 0.48 µM in HN3 and 5.8 µM in HN3-rslR cells, respectively^[1].

Western Blot Analysis^[1]

Cell Line:	HN3-rslR cells
Concentration:	0-8 μM
Incubation Time:	24 hours
Result:	Inhibited GPX4 expression, increased p62 and Nrf2 levels, and decreased Keap1 levels.

In Vivo

RSL3 (100 mg/kg, Intratumorally twice per week for 20 days) significantly inhibits the growth of tumor in combination with Trigonelline (HY-N0414) in mice bearing HN3R cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Ten-week-old athymic BALB/c male nude mice (nu/nu) bearing HN3R cells^[1]
Dosage:	100 mg/kg in combination with trigonelline (50 mg/kg)
Administration:	Intratumorally twice per week for 20 days
Result:	Significantly reduced the volume of tumor combined with trigonelline in mice.

Molecular Weight

440.88

Formula

C₂₃H₂₁ClN₂O₅

CAS No.

1219810-16-8

Appearance

Solid

Color

White to off-white

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (226.82 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.2682 mL	11.3410 mL	22.6819 mL
5 mM	0.4536 mL	2.2682 mL	4.5364 mL
10 mM	0.2268 mL	1.1341 mL	2.2682 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 5 mg/mL (11.34 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.67 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 3

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.72 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 4

Add each solvent one by one: 10% DMF 90% Corn Oil
Solubility: ≥ 0.56 mg/mL (1.27 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 20 mg/mL (45.36 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.90%

Select Batch:

Data Sheet (292 KB) SDS (393 KB)

COA (262 KB) HNMR (310 KB) RP-HPLC (244 KB) LCMS (94 KB) Elemental Analysis Report (120 KB)

Handling Instructions (2659 KB)

References

[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. [Content Brief]

[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. [Content Brief]

[3]. Zhang Z, et al., CGI1746 targets σ1R to modulate ferroptosis through mitochondria-associated membranes. Nat Chem Biol. 2024 Jan 11. [Content Brief]

[4]. Chen T, et al., Mitochondrial transplantation rescues neuronal cells from ferroptosis. Free Radic Biol Med. 2023 Nov 1;208:62-72. [Content Brief]

[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. [Content Brief]

[6]. Song H, et al., A potent GPX4 degrader to induce ferroptosis in HT1080 cells. Eur J Med Chem. 2024 Feb 5;265:116110. [Content Brief]

[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. [Content Brief]

[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. [Content Brief]

[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. [Content Brief]

[10]. Brown CW, et al., Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export. Dev Cell. 2019 Dec 2;51(5):575-586.e4. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.2682 mL	11.3410 mL	22.6819 mL	56.7048 mL
	5 mM	0.4536 mL	2.2682 mL	4.5364 mL	11.3410 mL
	10 mM	0.2268 mL	1.1341 mL	2.2682 mL	5.6705 mL
	15 mM	0.1512 mL	0.7561 mL	1.5121 mL	3.7803 mL
	20 mM	0.1134 mL	0.5670 mL	1.1341 mL	2.8352 mL
	25 mM	0.0907 mL	0.4536 mL	0.9073 mL	2.2682 mL
	30 mM	0.0756 mL	0.3780 mL	0.7561 mL	1.8902 mL
	40 mM	0.0567 mL	0.2835 mL	0.5670 mL	1.4176 mL
	50 mM	0.0454 mL	0.2268 mL	0.4536 mL	1.1341 mL
	60 mM	0.0378 mL	0.1890 mL	0.3780 mL	0.9451 mL
	80 mM	0.0284 mL	0.1418 mL	0.2835 mL	0.7088 mL
	100 mM	0.0227 mL	0.1134 mL	0.2268 mL	0.5670 mL

RSL3 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

RSL31219810-16-8(1S,3R)-RSL3RSL 3RSL-3p62Glutathione PeroxidaseFerroptosisReactive Oxygen SpeciesSequestosome-1SQSTM1Inhibitorinhibitorinhibit

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RSL3 (Synonyms: (1S,3R)-RSL3)

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Other Forms of RSL3:

RSL3 Related Antibodies

MedChemExpress Activity Verification

248 Publications Citing Use of MCE RSL3

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RSL3 Related Antibodies

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Complete Stock Solution Preparation Table

RSL3 Related Classifications

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