XJB-5-131
目录号 : GC64552
XJB-5-131 是一种靶向线粒体的 ROS 和电子清除剂。XJB-5-131 是双功能抗氧化剂，包含自由基清除剂。XJB-5-131 是针对线粒体的合成抗氧化剂。XJB-5-131 是有效的脐带血单核细胞 (CB MNC) 电离辐射保护剂和缓和剂。
Cas No.:866404-31-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
XJB-5-131 is a mitochondria-targeted ROS and electron scavenger[1]. XJB-5-131 is a bi-functional antioxidant that comprises a radical scavenger. XJB-5-131 is a synthetic antioxidant that targets mitochondria[2]. XJB-5-131 is an effective ionizing irradiation protector and mitigator of cord blood mononuclear cells (CB MNCs)[3].
XJB-5-131 also ameliorates hemorrhagic shock (HS)-induced activation of the pro-apoptotic enzymes, caspases 3 and 7, in ileal mucosa[1].XJB-5-131 reduces apoptosis and enhances cell survival in mouse embryonic cells in vitro[2].XJB-5-131 is a radiation protector for colony-forming unit-granulocyte macrophage (CFU-GM). XJB-5-131 is an effective mitigator when added after irradiation[3].
XJB-5-131 ameliorates peroxidation of the mitochondrial phospholipid, cardiolipin, in ileal mucosal samples from rats subjected to hemorrhagic shock (HS) [1].Intravenous treatment with XJB-5-131 (2 μmol/kg) significantly prolongs the survival of rats subjected to profound blood loss (33.5 mL/kg) despite administration of only a minimal volume of crystalloid solution (2.8 mL/kg) and the absence of blood transfusion[1].XJB-5-131 reduces oxidative damage to mitochondrial DNA, maintains mitochondrial DNA copy number, suppresses motor decline and weight loss, enhances neuronal survival, and improves mitochondrial function. XJB-5-131 significantly suppresses the disease phenotypes and improves mitochondrial function in a mouse model of Huntington's disease (HD) [2].XJB-5-131 (1 mg/kg; intraperitoneally injected; three times a week up to 57 weeks) suppresses decline of weight loss and motor function in a mouse model of HD[2].
[1]. Carlos A Macias, et al. Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock. Ann Surg. 2007 Feb;245(2):305-14.
[2]. Zhiyin Xun, et al. Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease. Cell Rep. 2012 Nov 29;2(5):1137-42.
[3]. Julie P Goff, et al. Evaluation of potential ionizing irradiation protectors and mitigators using clonogenic survival of human umbilical cord blood hematopoietic progenitor cells. Exp Hematol. 2013 Nov;41(11):957-66.
| Cas No. | 866404-31-1 | SDF | Download SDF |
| 分子式 | C53H81N7O9 | 分子量 | 960.25 |
| 溶解度 | DMSO : 125 mg/mL (130.17 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.0414 mL | 5.207 mL | 10.414 mL |
| 5 mM | 0.2083 mL | 1.0414 mL | 2.0828 mL |
| 10 mM | 0.1041 mL | 0.5207 mL | 1.0414 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury
Cell Death Dis 2020 Aug 14;11(8):629.PMID:32796819DOI:10.1038/s41419-020-02871-6.
Regulated necrosis has been reported to exert an important role in the pathogenesis of various diseases, including renal ischemia-reperfusion (I/R) injury. Damage to renal tubular epithelial cells and subsequent cell death initiate the progression of acute kidney injury (AKI) and subsequent chronic kidney disease (CKD). We found that ferroptosis appeared in tubular epithelial cells (TECs) of various human kidney diseases and the upregulation of tubular proferroptotic gene ACSL4 was correlated with renal function in patients with acute kidney tubular injury. XJB-5-131, which showed high affinity for TECs, attenuated I/R-induced renal injury and inflammation in mice by specifically inhibiting ferroptosis rather than necroptosis and pyroptosis. Single-cell RNA sequencing (scRNA-seq) indicated that ferroptosis-related genes were mainly expressed in tubular epithelial cells after I/R injury, while few necroptosis- and pyroptosis-associated genes were identified to express in this cluster of cell. Taken together, ferroptosis plays an important role in renal tubular injury and the inhibition of ferroptosis by XJB-5-131 is a promising therapeutic strategy for protection against renal tubular cell injury in kidney diseases.
XJB-5-131 Is a Mild Uncoupler of Oxidative Phosphorylation
J Huntingtons Dis 2022;11(2):141-151.PMID:35404288DOI:10.3233/JHD-220539.
Background: Mitochondria (MT) are energy "powerhouses" of the cell and the decline in their function from oxidative damage is strongly correlated in many diseases. To suppress oxygen damage, we have developed and applied XJB-5-131 as a targeted platform for neutralizing reactive oxygen species (ROS) directly in MT. Although the beneficial activity of XJB-5-131 is well documented, the mechanism of its protective effects is not yet fully understood. Objective: Here, we elucidate the mechanism of protection for XJB-5-131, a mitochondrial targeted antioxidant and electron scavenger. Methods: The Seahorse Flux Analyzer was used to probe the respiratory states of isolated mouse brain mitochondria treated with XJB-5-131 compared to controls. Results: Surprisingly, there is no direct impact of XJB-5-131 radical scavenger on the electron flow through the electron transport chain. Rather, XJB-5-131 is a mild uncoupler of oxidative phosphorylation. The nitroxide moiety in XJB-5-131 acts as a superoxide dismutase mimic, which both extracts or donates electrons during redox reactions. The electron scavenging activity of XJB-5-131 prevents the leakage of electrons and reduces formation of superoxide anion, thereby reducing ROS. Conclusion: We show here that XJB-5-131 is a mild uncoupler of oxidative phosphorylation in MT. The mild uncoupling property of XJB-5-131 arises from its redox properties, which exert a protective effect by reducing ROS-induced damage without sacrificing energy production. Because mitochondrial decline is a common and central feature of toxicity, the favorable properties of XJB-5-131 are likely to be useful in treating Huntington's disease and a wide spectrum of neurodegenerative diseases for which oxidative damage is a key component. The mild uncoupling properties of XJB-5-131 suggest a valuable mechanism of action for the design of clinically effective antioxidants.
A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington's Disease
J Huntingtons Dis 2022;11(1):3-15.PMID:34924397DOI:10.3233/JHD-210510.
Due to large increases in the elderly populations across the world, age-related diseases are expected to expand dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington's disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.
XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent
PLoS One 2018 Apr 9;13(4):e0194580.PMID:29630611DOI:10.1371/journal.pone.0194580.
We have reported that the radical scavenger XJB-5-131 attenuates or reverses progression of the disease phenotype in the HdhQ(150/150) mouse, a slow onset model of HD. Here, we tested whether XJB-5-131 has beneficial effects in R6/2 mice, a severe early onset model of HD. We found that XJB-5-131 has beneficial effects in R6/2 mice, by delaying features of the motor and histological phenotype. The impact was sex-dependent, with a stronger effect in male mice. XJB-5-131 treatment improved some locomotor deficits in female R6/2 mice, but the effects were, in general, greater in male mice. Chronic treatment of male R6/2 mice with XJB-5-1-131 reduced weight loss, and improved the motor and temperature regulation deficits, especially in male mice. Treatment with XJB-5-131 had no effect on the lifespan of R6/2 mice. Nevertheless, it significantly slowed somatic expansion at 90 days, and reduced the density of inclusions. Our data show that while treatment with XJB-5-131 had complex effects on the phenotype of R6/2 mice, it produced a number of significant improvements in this severe model of HD.
Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes
Hum Mol Genet 2016 May 1;25(9):1792-802.PMID:26908614DOI:10.1093/hmg/ddw051.
Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.