MitoTEMPOL
目录号 : GC44207A mitochondrial-targeting SOD mimetic
Cas No.:1101113-39-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MitoTEMPOL is a mitochondria-targeting superoxide dismutase mimetic that reduces mitochondrial O2- to H2O2. Like the related compound MitoTEMPO , MitoTEMPOL combines an antioxidant moiety (here, TEMPOL, also known as 4-hydroxy-TEMPO) with the lipophilic cation triphenylphosphonium, which allows it to pass through lipid bilayers and accumulate in mitochondria. MitoTEMPOL has been used to elucidate the role of mitochondria-derived superoxide in mitochondrial, cellular, and whole animal signaling.
| Cas No. | 1101113-39-6 | SDF | |
| Canonical SMILES | [O]N1C(C)(C)CC(OCCCCC[P+](C2=CC=CC=C2)(C3=CC=CC=C3)C4=CC=CC=C4)CC1(C)C.[Br-] | ||
| 分子式 | C32H42NO2P•Br | 分子量 | 583.6 |
| 溶解度 | DMF: 50 mg/ml,DMSO: 50 mg/ml,Ethanol: 50 mg/ml,PBS (pH 7.2): 10 mg/ml | 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 | 1.7135 mL | 8.5675 mL | 17.135 mL |
| 5 mM | 0.3427 mL | 1.7135 mL | 3.427 mL |
| 10 mM | 0.1714 mL | 0.8568 mL | 1.7135 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。
MitoTEMPOL modulates mitophagy and histopathology of Wistar rat liver after streptozotocin injection
Iran J Basic Med Sci 2022 Nov;25(11):1382-1388.PMID:36474569DOI:10.22038/IJBMS.2022.65285.14375.
Objectives: This study aims to explore the effect of MitoTEMPOL on histopathology, lipid droplet, and mitophagy gene expression of Wistar rat's liver after injection of streptozotocin (STZ). Materials and methods: Twenty male Wistar rats were divided into 4 groups: Control (n=5); 100 mg/kg BW/day MitoTEMPOL orally (n=5); 50 mg/kg BW STZ intraperitoneal injection (n=5); and MitoTEMPOL+STZ (n=5). STZ was given a single dose, while MitoTEMPOL was given for 5 weeks after 1 week of STZ injection. Histopathological appearance, lipid droplets, mitophagy, and autophagy gene expression were examined after the MitoTEMPOL treatment. Results: We found metabolic zone shifting that might be correlated with the liver activity of fatty acid oxidation in the STZ group, a decrease of lipid droplets in MitoTEMPOL and MitoTEMPOL + STZ compared with Control and STZ groups were found in this study. We also found significant changes in PINK1, Parkin, BNIP3, Mfn1, and LC3 gene expression, but no difference in Opa1, Fis1, Drp1, and p62 gene expression, suggesting a change of mitochondrial fusion rather than mitochondrial fission correlated with mitophagy. Conclusion: All this concluded that MitoTEMPOL could act as a modulator of mitophagy and metabolic function of the liver, thus amplifying its crucial role in preventing mitochondrial damage in the liver in the early onset of diabetes mellitus.
MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction
Am J Physiol Lung Cell Mol Physiol 2020 Aug 1;319(2):L228-L238.PMID:32460519DOI:10.1152/ajplung.00473.2019.
Clinical studies indicate that sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis-induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation; we therefore hypothesized that therapies that target mitochondrial free radical production may prevent sepsis-induced diaphragm weakness. The present study determined whether MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis-induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: 1) sham-operated controls, 2) animals with sepsis induced by cecal ligation puncture (CLP), 3) sham controls given MitoTEMPOL (10 mg·kg-1·day-1 ip), and 4) CLP animals given MitoTEMPOL. At 48 h after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 h) on CLP-induced diaphragm weakness. The effects of MitoTEMPOL on cytokine-mediated alterations on muscle cell superoxide generation and cell size in vitro were also assessed. Sepsis markedly reduced diaphragm force generation. Both immediate and delayed MitoTEMPOL administration prevented sepsis-induced diaphragm weakness. MitoTEMPOL reversed sepsis-mediated reductions in mitochondrial function, activation of proteolytic pathways, and decreases in MHC content. Cytokines increased muscle cell superoxide generation and decreased cell size, effects that were ablated by MitoTEMPOL. MitoTEMPOL and other compounds that target mitochondrial free radical generation may be useful therapies for sepsis-induced diaphragm weakness.
MitoTEMPOL Inhibits ROS-Induced Retinal Vascularization Pattern by Modulating Autophagy and Apoptosis in Rat-Injected Streptozotocin Model
Life (Basel) 2022 Jul 15;12(7):1061.PMID:35888150DOI:10.3390/life12071061.
Diabetic retinopathy leads to retinal malfunction, blindness, and reduced quality of life in adult diabetes patients. The involvement of reactive oxygen species (ROS) regulation stimulated by high blood glucose levels opens the opportunity for ROS modulator agents such as MitoTEMPOL. This study aims to explore the effect of MitoTEMPOL on ROS balance that may be correlated with retinal vascularization pattern, autophagy, and apoptosis in a streptozotocin-induced rat model. Four groups of male Wistar rats (i.e., control, TEMPOL (100 mg/kg body weight [BW]), diabetic (streptozotocin, 50 mg/kg BW single dose), and diabetic + TEMPOL; n = 5 for each group) were used in the study. MitoTEMPOL was given for 5 weeks, followed by funduscopy, and gene and protein expression were explored from the rat's retina. Streptozotocin injection decreased bodyweight and increased food and water intake, as well as fasting blood glucose. The results showed that MitoTEMPOL reduced retinal vascularization pattern and decreased superoxide dismutase gene expression and protein carbonyl, caspase 3, and caspase 9 protein levels. A modulation of autophagy in diabetes that was reversed in the diabetic + TEMPOL group was found. In conclusion, MitoTEMPOL modulation on autophagy and apoptosis contributes to its role as a potent antioxidant to prevent diabetic retinopathy by inhibiting ROS-induced retinal vascularization patterns.
Antioxidant properties of MitoTEMPOL and its hydroxylamine
Free Radic Res 2009 Jan;43(1):4-12.PMID:19058062DOI:10.1080/10715760802582183.
Piperidine nitroxides such as TEMPOL have been widely used as antioxidants in vitro and in vivo. MitoTEMPOL is a mitochondria-targeted derivative of TEMPOL designed to protect mitochondria from the oxidative damage that they accumulate, but once there is rapidly reduced to its hydroxylamine, MitoTEMPOL-H. As little is known about the antioxidant efficacy of hydroxylamines, this study has assessed the antioxidant activity of both MitoTEMPOL and MitoTEMPOL-H. The hydroxylamine was more effective at preventing lipid-peroxidation than MitoTEMPOL and decreased oxidative damage to mitochondrial DNA caused by menadione. In contrast to MitoTEMPOL, MitoTEMPOL-H has no superoxide dismutase activity and its antioxidant actions are likely to be mediated by hydrogen atom donation. Therefore, even though MitoTEMPOL is rapidly reduced to MitoTEMPOL-H in cells, it remains an effective antioxidant. Furthermore, as TEMPOL is also reduced to a hydroxylamine in vivo, many of its antioxidant effects may also be mediated by its hydroxylamine.
A novel HIF-2α targeted inhibitor suppresses hypoxia-induced breast cancer stemness via SOD2-mtROS-PDI/GPR78-UPRER axis
Cell Death Differ 2022 Sep;29(9):1769-1789.PMID:35301432DOI:10.1038/s41418-022-00963-8.
Hypoxic tumor microenvironment (TME) plays critical roles in induction of cancer stem cell-like phenotype in breast cancer and contribute to chemoresistance. However, the mechanism underlying stemness reprogramming of breast cancer cells (BCs) by hypoxic TME remains largely unknown. In the present study, we illustrated that HIF-2α, but not HIF-1α, induces stemness in BCs under hypoxia through SOD2-mtROS-PDI/GRP78-UPRER pathway, linking mitochondrial metabolic state to endoplasmic reticulum (ER) response via mitochondrial reactive oxygen species (mtROS) level. HIF-2α activates endoplasmic reticulum unfolded protein response (UPRER) in drug-sensitive MCF7 and T47D cells to induce drug-resistant stem-like phenotype. Genetic depletion or pharmacological inhibition (YQ-0629) of HIF-2α abolished hypoxia-induced stem-like phenotype in vitro and in vivo. Mechanistically, HIF-2α activates transcription of superoxide dismutase 2 (SOD2) under hypoxia and thereby decreases mtROS level. With less mtROS transported to endoplasmic reticulum, the expression and activity of protein disulfide isomerase (PDI) is suppressed, allowing glucose-regulated protein 78 (GRP78) to dissociate from receptor proteins of UPRER and bind misfolded protein to activate UPRER, which eventually confer chemoresistance and stem-like properties to BCs. Moreover, the increase in mtROS and PDI levels caused by HIF-2α knockdown and the subsequent UPRER inhibition could be substantially rescued by MitoTEMPOL (a mtROS scavenger), 16F16 (a PDI inhibitor), or GRP78 overexpression. Overall, we reported the critical roles of HIF-2α-SOD2-mtROS-PDI/GRP78-UPRER axis in mediating hypoxia-induced stemness in BCs, highlighting the interaction between organelles and providing evidence for further development of targeted HIF-2α inhibitor as a promising therapeutic strategy for chemoresistant breast cancer.