| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
Mitochondria; Reactive Oxygen Species (ROS); Electron scavenging. XJB-5-131 targets mitochondria through its lipophilic cationic vector (based on gramicidin S). Once inside the mitochondrial matrix, the nitroxide moiety mimics superoxide dismutase (SOD), participating in redox reactions to neutralize superoxide (O2•-) and other ROS. It also scavenges lipid peroxyl radicals, preventing chain reactions of lipid peroxidation. It inhibits ferroptosis by preventing the iron-dependent peroxidation of cardiolipin, a mitochondrial phospholipid.
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| ln Vitro |
Additionally, XJB-5-131 enhances the activation of caspases 3 and 7, two proapoptotic enzymes, in the ileal mucosa when hemorrhagic shock (HS) is applied [1]. In vitro, XJB-5-131 enhances cell survival and decreases apoptosis in mouse embryonic cells [2]. A radioprotectant for colony-forming units granulocyte macrophages (CFU-GM) is XJB-5-131. When applied after radiation, XJB-5-131 functions as an efficient moderator [3].
In vitro, XJB-5-131 (EC50 68-114 nM) potently inhibits ferroptosis induced by system xc- inhibitors or GPX4 inhibitors (e.g., FINO2, 10 uM) in HT-1080 cells (100% viability at 200 nM). It reduces oxidative damage to mitochondrial DNA (mtDNA), maintains mtDNA copy number, and enhances neuronal survival in cell models. It prevents cardiolipin peroxidation (a key mitochondrial lipid) in ileal cells. It is a potent antioxidant with ~39-fold greater anti-ferroptotic efficacy than JP4-039. |
| ln Vivo |
In rats suffering from hemorrhagic shock (HS), XJB-5-131 enhances the peroxidation of cardiolipin and mitochondrial phospholipids in ileal mucosal samples[1]. Even though only a little amount of crystalloid solution (2.8 mL/kg) and no blood transfusion were given, rats with severe blood loss had a much longer survival rate (33.5 mL/kg) after receiving an intravenous injection of XJB-5-131 (2 μMol/kg)[1]. XJB-5-131 promotes mitochondrial function, prevents weight loss and oxidative damage to mitochondrial DNA, preserves the number of copies of mitochondrial DNA, increases neuronal survival, and improves exercise capacity. In a mouse model of Huntington's disease (HD), XJB-5-131 dramatically suppresses the disease phenotype and enhances mitochondrial function[2]. In HD mice models, XJB-5-131 (1 mg/kg; intraperitoneal injection; three times per week for up to 57 weeks) prevents weight loss and the deterioration of motor function[2].
In vivo, XJB-5-131 (e.g., 2 mg/kg, i.p. or i.v.) crosses the blood-brain barrier (BBB) and is visualized in the brains of rats. In a knockin mouse model of Huntington's disease (HD), XJB-5-131 suppresses motor decline, inhibits weight loss, reduces mtDNA damage, improves mitochondrial function, and enhances neuronal survival. It is an effective mitigator of ionizing radiation when added after irradiation and prolongs survival in rats subjected to massive blood loss. It has a single-dose radioprotection effect lasting 5 days in vivo. |
| Enzyme Assay |
Ferroptosis inhibition assay: Treat HT-1080 cells with XJB-5-131 (0-500 nM) for 1 hour, then induce ferroptosis with FINO2 (10 uM) or erastin. After 24 hours, measure cell viability via CellTiter-Glo or calcein-AM staining. Calculate EC50 (68-114 nM). For lipid peroxidation, treat cells with XJB-5-131, then measure C11-BODIPY581/591 oxidation by flow cytometry (shift from red to green fluorescence). For cardiolipin peroxidation, extract lipids and analyze by LC-MS/MS.
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| Cell Assay |
Cell Viability Assay[3]
Cell Types: Low density mononuclear cells (MNC) Tested Concentrations: 10 μM Incubation Duration:Added to cells one hour before irradiation or immediately after irradiation Experimental Results: Was a protector when given before irradiation as shown by an increase in the D0 to 1.93±0.13 for CFU-GM with XJB-5-131. MTT/CCK-8 viability assay: Seed cells in 96-well plates. Pre-treat with XJB-5-131 (40 nM-2 uM) for 1-2 hours, then expose to stressors: H2O2 (100-200 uM), erastin (1 uM), or ionizing radiation (5-10 Gy). Incubate for 24-72 hours. Measure absorbance. For mitochondrial function, use JC-1 or TMRM staining to measure mitochondrial membrane potential (deltaΨm). For mtDNA damage, perform qPCR of long mitochondrial DNA fragments. Maintain concentrations typical range: 40 nM-2 uM for cultures. |
| Animal Protocol |
Animal/Disease Models: Male specific pathogen-free SD (Sprague-Dawley) rats, weighing 150 to 250 g[1]
Doses: 2 μmol/kg Route of Administration: Administered intravenously (iv) using a syringe pump Experimental Results: The rats treated with XJB-5-131 survived Dramatically longer ( P < 0.01). Three of six survived for longer than 3 hrs (hours) after completion of the hemorrhage protocol and one rat survived for the whole 6 hrs (hours) postbleeding observation period. Animal/Disease Models: HD150KI mice[2] Doses: 1 mg/kg Route of Administration: intraperitoneally (ip) injected; three times a week up to 57 weeks Experimental Results: Chronic treatment suppressed weight loss. Increased the average body mass by 22%. Mouse Huntington's Disease model: Use R6/2 or Q175 knock-in HD mice. Administer XJB-5-131 (2 mg/kg, i.p. or i.v.) 3 times per week for 4-8 weeks. Monitor body weight, motor coordination (rotarod, grip strength, clasping), and survival. At endpoint, harvest brain and muscle. Measure mtDNA copy number via qPCR. Assess striatal neuron survival via stereology (NeuN staining). Measure mitochondrial function (complex I/II/IV activity). For radiation protection: Irradiate mice (9-10 Gy total body). Administer XJB-5-131 (2 mg/kg) before or after irradiation. Assess survival and hematopoietic recovery. |
| ADME/Pharmacokinetics |
XJB-5-131: Molecular formula C₅3H₈1N₇O₉. Molecular weight: 960.25 g/mol. Appearance: Yellow to orange solid. Solubility: Soluble in DMSO (≥10 mg/mL). Storage: Store powder at -20degC, protected from light. In solution, store at -80degC for up to 6 months. Avoid repeated freeze-thaw cycles. Pharmacokinetics: In mice, plasma, kidney, liver, and brain levels can be measured by LC-MS/MS. It achieves ~600-fold mitochondrial enrichment. It does not affect mitochondrial membrane potential, as it is charge-neutral. Half-life in vivo is short but effective.
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| Toxicity/Toxicokinetics |
XJB-5-131 is generally well-tolerated in animal models at doses up to 2-5 mg/kg. No acute toxicity has been reported in HD mice at these doses. It is a potent ferroptosis inhibitor and protects normal tissues from radiation damage. However, chronic safety studies are limited. Standard safety precautions for handling synthetic chemicals should be observed. Not approved for human use. It is a research-use-only compound. Always consult the SDS. Not for therapeutic use. Wear gloves and lab coat.
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| References |
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| Additional Infomation |
See also: Xjb-5-131 (comment moved to).
XJB-5-131 is a derivative of the antibiotic gramicidin S, repurposed as a mitochondria-targeted antioxidant. It is one of the most potent and well-studied mitochondrial ROS scavengers in the literature. It is particularly valuable for studying ferroptosis in neurodegenerative diseases (Huntington's, Alzheimer's, Parkinson's) and ischemia-reperfusion injury (stroke, heart attack). It is a powerful tool for investigating the role of mitochondrial oxidative stress in aging. Its ability to cross the BBB without disrupting membrane potential is a key advantage. It is also available as a research chemical. |
| Molecular Formula |
C53H80N7O9
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|---|---|
| Molecular Weight |
959.24
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| Exact Mass |
959.609
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| CAS # |
866404-31-1
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| PubChem CID |
89059932
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| Appearance |
White to off-white solid powder
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| LogP |
7.8
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
69
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| Complexity |
1700
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C1CC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCNC(=O)OCC2=CC=CC=C2)C(NC2CC(C)(C)N([O-])C(C2)(C)C)=O)=O)C(C)C)N1C(=O)[C@H](/C=C/[C@H](CC(C)C)NC(=O)OC(C)(C)C)CC1C=CC=CC=1
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| InChi Key |
VTYPGEHUYSBZTQ-VQPCLXHQSA-N
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| InChi Code |
InChI=1S/C53H81N7O9/c1-35(2)30-40(56-50(66)69-51(5,6)7)27-26-39(31-37-20-14-12-15-21-37)48(64)59-29-19-25-43(59)46(62)58-44(36(3)4)47(63)57-42(24-18-28-54-49(65)68-34-38-22-16-13-17-23-38)45(61)55-41-32-52(8,9)60(67)53(10,11)33-41/h12-17,20-23,26-27,35-36,39-44,67H,18-19,24-25,28-34H2,1-11H3,(H,54,65)(H,55,61)(H,56,66)(H,57,63)(H,58,62)/b27-26+/t39-,40-,42+,43+,44+/m1/s1
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| Chemical Name |
tert-butyl N-[(E,4S,7S)-7-benzyl-8-[(2S)-2-[[(2S)-1-[[(2S)-1-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino]-1-oxo-5-(phenylmethoxycarbonylamino)pentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate
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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) |
DMSO: 125 mg/mL (130.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0425 mL | 5.2125 mL | 10.4249 mL | |
| 5 mM | 0.2085 mL | 1.0425 mL | 2.0850 mL | |
| 10 mM | 0.1042 mL | 0.5212 mL | 1.0425 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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