| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
(1R,3S)-RSL3 targets cell death pathways, primarily through interaction with glutathione peroxidase 4 (GPX4), though with greatly reduced potency compared to the active (1S,3R) enantiomer. GPX4 is a selenoenzyme that reduces lipid hydroperoxides and protects cells from ferroptosis. By inhibiting GPX4, RSL3 and its analogs induce the accumulation of lipid peroxides and trigger ferroptotic cell death. The (1R,3S) enantiomer serves as an inactive or weakly active control.
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| ln Vitro |
In vitro, (1R,3S)-RSL3 induces cell death in HT22 wild-type cells with an EC50 of 5.2 µM, while the active enantiomer RSL3 ((1S,3R)-RSL3) has an EC50 of 0.004 µM. In HT22 Bid CRISPR KO cells, (1R,3S)-RSL3 induces cell death with an EC50 of 28.8 µM. The compound is used as a negative control in ferroptosis studies to differentiate GPX4-dependent effects from off-target effects. The >1,000-fold difference in potency between enantiomers demonstrates the stereospecificity of GPX4 inhibition.
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| ln Vivo |
In vivo, (1R,3S)-RSL3 is used as a control compound in studies investigating ferroptosis and its role in various diseases, including cancer and neurodegeneration. As the less active enantiomer, it does not induce ferroptosis at concentrations where RSL3 is active, making it valuable for confirming the specificity of ferroptotic effects. However, specific in vivo efficacy data for (1R,3S)-RSL3 have not been detailed in the available literature.
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| Enzyme Assay |
For in vitro GPX4 inhibition assays, recombinant GPX4 protein is incubated with glutathione, lipid hydroperoxide substrate, and varying concentrations of the test compound (0.001-100 µM). Enzyme activity is measured by monitoring the consumption of glutathione or the reduction of hydroperoxide using colorimetric or fluorometric assays. IC50 values for GPX4 inhibition are calculated by fitting dose-response curves. The (1R,3S) enantiomer shows much weaker inhibition than the active (1S,3R) enantiomer.
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| Cell Assay |
For cell viability assays, HT22 hippocampal cells are seeded in 96-well plates and treated with (1R,3S)-RSL3 at concentrations ranging from 0.1 nM to 100 µM for 16 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays. EC50 values are calculated from dose-response curves. For ferroptosis characterization, lipid peroxidation can be measured using fluorescent probes such as C11-BODIPY 581/591, and intracellular glutathione levels can be quantified.
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| Animal Protocol |
For in vivo studies, (1R,3S)-RSL3 can be administered to mice via intraperitoneal or intravenous injection. Tissues are collected for histological analysis and measurement of lipid peroxidation markers. However, specific in vivo protocols for this compound have not been detailed in the literature. As a control compound, it may be used alongside the active RSL3 enantiomer in tumor xenograft or disease models to confirm ferroptosis-specific effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (1R,3S)-RSL3 have not been characterized in the available literature. The compound is soluble in DMSO and other organic solvents. Storage is recommended at -20°C for long-term stability. As a research compound, it is not intended for therapeutic use. Further PK studies would be required for any in vivo applications.
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| Toxicity/Toxicokinetics |
Toxicological data for (1R,3S)-RSL3 are limited to in vitro cytotoxicity assessments. At the concentrations used for control experiments (up to 100 µM), the compound is cytotoxic to HT22 cells with an EC50 of 5.2 µM. The compound is for research use only and is not intended for human or veterinary use. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
(1R,3S)-2-(2-chloro-1-oxoethyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylic acid methyl ester is a Halman alkaloid.
(1R,3S)-RSL3 is the less active enantiomer of RSL3, a potent GPX4 inhibitor and ferroptosis inducer. While (1S,3R)-RSL3 has an EC50 of 0.004 µM in HT22 cells, the (1R,3S) enantiomer has an EC50 of 5.2 µM, demonstrating >1,000-fold lower potency. The compound is used as a control reagent for studying ferroptosis mechanisms. (1R,3S)-RSL3 is a research tool and is not approved for clinical use. |
| Molecular Formula |
C23H21CLN2O5
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|---|---|
| Molecular Weight |
440.876245260239
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| Exact Mass |
440.113
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| CAS # |
1219810-13-5
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| PubChem CID |
40911229
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
696
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC(=O)[C@@H]1CC2=C([C@H](N1C(=O)CCl)C3=CC=C(C=C3)C(=O)OC)NC4=CC=CC=C24
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| InChi Key |
TXJZRSRTYPUYRW-GHTZIAJQSA-N
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| InChi Code |
InChI=1S/C23H21ClN2O5/c1-30-22(28)14-9-7-13(8-10-14)21-20-16(15-5-3-4-6-17(15)25-20)11-18(23(29)31-2)26(21)19(27)12-24/h3-10,18,21,25H,11-12H2,1-2H3/t18-,21+/m0/s1
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| Chemical Name |
methyl (1R,3S)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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