Elamipretide (MTP-131)
(Synonyms: D-精氨酰-2,6-二甲基-L-酪氨酰-L-赖氨酰-L-苯丙氨酰胺,RX-31; SS-31) 目录号 : GC30014
Elamipretide (MTP-131), as a water-soluble tetrapeptide, can enhance cellular ATP synthesis to improve electron transport and reduce the formation of ROS.
Cas No.:736992-21-5
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
| Cell experiment [1]: | |
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Cell lines |
RGC-5 cells |
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Preparation Method |
MTP-131 pretreatment and induction of oxidative stress RGC-5 cells were seeded at a density of 1×104 cells/well in 6-well plates and incubated in 5% CO2 at 37°C for 24 h. Cells at approximately 70% confluence were pretreated with 0.01, 0.1 or 1 µM MTP-131 in serum-free DMEM at 37°C for 1 h and then rinsed twice with PBS. Then, RGC-5 cells were exposed to 500 µM H2O2 in serum-free DMEM for 24 h to induce a sustained oxidative stress in vitro. |
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Reaction Conditions |
0.01, 0.1 or 1 µM; at 37°C for 1 h |
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Applications |
Pretreatment of cells with MTP-131 inhibited H2O2-induced cytotoxicity and reduced LDH release in a dose-dependent manner, compared with cells treated with H2O2 alone. Mitochondrial depolarization and ROS generation were also prevented by MTP-131 pretreatment. In addition, MTP-131 pretreatment inhibited cytochrome c release from mitochondria to cytoplasm, and significantly reduced apoptosis in RGC-5 cells, compared with cells treated with H2O2 alone. |
| Animal experiment [2]: | |
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Animal models |
Dogs |
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Preparation Method |
14 dogs with microembolization-induced HF (heart failure) were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (Control, HF-CON, n=7). LV ejection fraction (EF), plasma n-terminal pro-brain natriuretic peptide (nt-pro BNP), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) were measured before (pre-treatment) and 3 months after initiating therapy (post-treatment). MITO respiration, membrane potential (δψm), maximum rate of ATP synthesis and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. |
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Dosage form |
0.5 mg/kg once daily; s.c. |
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Applications |
Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers and reverses MITO abnormalities in LV myocardium of dogs with advanced HF. |
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References: [1]Chen M, et al. Protective effect of mitochondria?targeted peptide MTP?131 against oxidative stress?induced apoptosis in RGC?5 cells. Mol Med Rep. 2017 Apr;15(4):2179-2185. | |
Elamipretide (MTP-131), as a water-soluble tetrapeptide, can enhance cellular ATP synthesis to improve electron transport and reduce the formation of ROS. And it inhibits lipid peroxidation and prevents mitochondrial swelling, aiding in mitochondrial protection[1][2].
In vitro experiment it exhibited that treatment with 1 µM elamipretide in cultured ARPE-19 cells results in accelerating an increase in mitochondrial volume[3]. In vitro, added in the freeze media with 1 and 10 µM Elamipretide obviously improved post-thaw sperm parameters including motility and viability, stability of the plasma membrane, and mitochondria and chromosomes[4]. In control INS1 cells, treatment with 1 µM Elamipretide for 20 h suffiently increase the engulfment of mitochondria into autophagosomes, but it has no increase at 10 µM Elamipretide, suggesting a complete reversal of mitochondrial fragmentation induced by nutrient excess at 10 µM, while not being complete at 1 µM[5].
In vivo, 1 mg/kg MTP-131 treatment reversed visual decline without improving glycemic control or reducing bodyweight in diabetic mouse models[6]. In vivo test it shown that treatment repeatly with 5 mg/kg elamipretide intraperitoneally in mice provided maximum neuroprotective effects without any adverse effects[7]. Moreover, treatment with 3 mg/kg/day SS-31 (elamipretide) restored redox homeostasis, improved mitochondrial quality, and increased exercise tolerance without an increase in mitochondrial content in aged mice[8].
Dai DF, et al. Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Circ Heart Fail. 6:1067-1076.
Zhao K, et al., 2005. Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. Biochem Pharma. 70:1796-1806.
Grosser JA, et al. The effects of a mitochondrial targeted peptide (elamipretide/SS31) on BAX recruitment and activation during apoptosis. BMC Res Notes. 2021 May 22;14(1):198.
Bai H, et al. Elamipretide as a potential candidate for relieving cryodamage to human spermatozoa during cryopreservation. Cryobiology. 2020 Aug;95:138-142.
Petcherski A, et al. Elamipretide Promotes Mitophagosome Formation and Prevents Its Reduction Induced by Nutrient Excess in INS1 β-cells. J Mol Biol. 2018 Dec 7;430(24):4823-4833.
Alam NM, et al. A mitochondrial therapeutic reverses visual decline in mouse models of diabetes. Dis Model Mech. 2015 Jul 1;8(7):701-10.
Zhao W, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation. 2019 Nov 20;16(1):230.
Campbell MD, et al. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 2019 Apr;134:268-281.
References:
Elamipretide (MTP-131) 作为一种水溶性四肽，可以增强细胞 ATP 合成，从而改善电子传输并减少 ROS 的形成。并抑制脂质过氧化，防止线粒体肿胀，有助于保护线粒体[1][2]。
体外实验表明， 1 µ；培养的 ARPE-19 细胞中的 M elamipretide 导致线粒体体积加速增加[3]。在体外，在冷冻培养基中添加 1 和 10 µM Elamipretide 显着改善了解冻后的精子参数，包括运动性和活力、质膜稳定性以及线粒体和染色体[4]。在对照 INS1 细胞中，用 1 77777#181;M Elamipretide 处理 20 小时足以增加线粒体被自噬体吞噬，但在 10 µM Elamipretide 时没有增加，表明在 10 &88188881 时营养过剩诱导的线粒体断裂完全逆转;M，虽然在 1 µ 处未完成；M[5]。
在体内，1 mg/kg MTP-131 治疗可逆转视力下降，但不会改善血糖控制或减少糖尿病小鼠模型的体重[6]。体内试验表明，在小鼠腹腔内重复使用 5 mg/kg elamipretide 进行治疗可提供最大的神经保护作用，且无任何不良反应[7]。此外，用 3 mg/kg/天的 SS-31（elamipretide）治疗可恢复氧化还原稳态、改善线粒体质量并增加运动耐量，而不会增加老年小鼠的线粒体含量[8]。
Dai DF, et al.压力过载引起的心力衰竭的全球蛋白质组学和通路分析及其通过线粒体靶向肽的衰减。 Circ 心脏衰竭。 6:1067-1076。
Zhao K, et al., 2005. 线粒体靶向肽可防止神经元细胞系中叔丁基氢过氧化物诱导的线粒体去极化和细胞凋亡。生化制药。 70:1796-1806。
Grosser JA 等。线粒体靶向肽 (elamipretide/SS31) 对细胞凋亡过程中 BAX 募集和激活的影响。 BMC Res 注释。 2021 年 5 月 22 日；14(1):198。
Bai H, et al. Elamipretide 作为减轻低温保存过程中对人类精子的低温损伤的潜在候选药物。低温生物学。 2020 年 8 月；95:138-142。
Petcherski A 等人。 Elamipretide 在 INS1 β-细胞中促进线粒体吞噬体形成并防止其因营养过剩而减少。 J Mol Biol。 2018 年 12 月 7 日；430(24):4823-4833。
Alam NM 等。线粒体疗法可逆转糖尿病小鼠模型的视力下降。 Dis 模型机械。 2015 年 7 月 1 日；8(7):701-10。
赵伟等。 Elamipretide (SS-31) 改善小鼠中由脂多糖诱导的线粒体功能障碍、突触和记忆障碍。 J 神经炎症。 2019 年 11 月 20 日；16(1):230。
坎贝尔医学博士等。用 SS-31 改善线粒体功能可逆转与年龄相关的氧化还原应激并提高老年小鼠的运动耐量。自由基生物学医学。 2019 年 4 月；134:268-281。
| Cas No. | 736992-21-5 | SDF | |
| 别名 | D-精氨酰-2,6-二甲基-L-酪氨酰-L-赖氨酰-L-苯丙氨酰胺,RX-31; SS-31 | ||
| Canonical SMILES | {d-Arg}-Dmt-Lys-Phe-NH2 | ||
| 分子式 | C32H49N9O5 | 分子量 | 639.79 |
| 溶解度 | DMSO : ≥ 29 mg/mL (45.33 mM) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.563 mL | 7.8151 mL | 15.6301 mL |
| 5 mM | 0.3126 mL | 1.563 mL | 3.126 mL |
| 10 mM | 0.1563 mL | 0.7815 mL | 1.563 mL |
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Mitochondrial targeted therapy with Elamipretide (MTP-131) as an adjunct to tumor necrosis factor inhibition for traumatic optic neuropathy in the acute setting
Exp Eye Res 2020 Oct;199:108178.32758490 PMC7554259
Traumatic optic neuropathy (TON) can occur following blunt trauma to the orbit and can lead to permanent vision loss. In this study, we investigated the effectiveness of Elamipretide (MTP-131), a small mitochondrially-targeted tetrapeptide, in conjunction with etanercept, a tumor necrosis factor (TNF) inhibitor, as neuroprotective agents of retinal ganglion cells (RGCs) after optic nerve trauma with sonication-induced TON (SI-TON) in mice. Treatment with intravitreal MTP-131 and subcutaneous etanercept and MTP-131 showed a 21% increase (p < 0.01) in RGC survival rate compared to PBS-treated control eyes. Subcutaneous etanercept and MTP-131 had an 11% increase (p < 0.05) in RGC survival compared to controls. Subcutaneous etanercept only group showed 20% increase (p < 0.01) in RGC survival compared to controls, while subcutaneous MTP-131 alone showed a 17% increase (p < 0.01). Surprisingly, we did not observe a synergistic effect between the two drugs in the group receiving both etanercept and MTP-131. One possible explanation for the absence of a synergistic effect is that MTP-131 and etanercept may be acting on different portions of the same pathway.
Restoring mitochondrial superoxide levels with Elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease
J Biol Chem 2020 May 22;295(21):7249-7260.32277051 PMC7247302
Exposure to chronic hyperglycemia because of diabetes mellitus can lead to development and progression of diabetic kidney disease (DKD). We recently reported that reduced superoxide production is associated with mitochondrial dysfunction in the kidneys of mouse models of type 1 DKD. We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-derived metabolites in their urine. Here we examined renal superoxide production in a type 2 diabetes animal model, the db/db mouse, and the role of a mitochondrial protectant, MTP-131 (also called elamipretide, SS-31, or Bendavia) in restoring renal superoxide production and ameliorating DKD. We found that 18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2 Administration of MTP-131 significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling.
Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice
J Neuroinflammation 2019 Nov 20;16(1):230.31747905 PMC6865061
Background: It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of Elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. Methods: We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. Results: Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with Elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, Elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. Conclusion: These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant Elamipretide. Consequently, Elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.
Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure
Circ Heart Fail 2016 Feb;9(2):e002206.26839394 PMC4743543
Background: Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial function in dogs with heart failure (HF). Methods and results: Fourteen dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (control, HF-CON, n=7). LV ejection fraction, plasma n-terminal pro-brain natriuretic peptide, tumor necrosis factor-α, and C-reactive protein were measured before (pretreatment) and 3 months after initiating therapy (post-treatment). Mitochondrial respiration, membrane potential (Δψm), maximum rate of ATP synthesis, and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, ejection fraction decreased at post-treatment compared with pretreatment (29 ± 1% versus 31 ± 2%), whereas in HF+ELA dogs, ejection fraction significantly increased at post-treatment compared with pretreatment (36 ± 2% versus 30 ± 2%; P<0.05). In HF-CON, n-terminal pro-brain natriuretic peptide increased by 88 ± 120 pg/mL during follow-up but decreased significantly by 774 ± 85 pg/mL in HF+ELA dogs (P<0.001). Treatment with elamipretide also normalized plasma tumor necrosis factor-α and C-reactive protein and restored mitochondrial state-3 respiration, Δψm, rate of ATP synthesis, and ATP/ADP ratio (ATP/ADP: 0.38 ± 0.04 HF-CON versus 1.16 ± 0.15 HF+ELA; P<0.001). Conclusions: Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF.
Advances in primary mitochondrial myopathies
Curr Opin Neurol 2019 Oct;32(5):715-721.31408013 PMC6938233
Purpose of review: Although mitochondrial diseases impose a significant functional limitation in the lives of patients, treatment of these conditions has been limited to dietary supplements, exercise, and physical therapy. In the past few years, however, translational medicine has identified potential therapies for these patients. Recent findings: For patients with primary mitochondrial myopathies, preliminary phase I and II multicenter clinical trials of Elamipretide indicate safety and suggest improvement in 6-min walk test (6MWT) performance and fatigue scales. In addition, for thymidine kinase 2-deficient (TK2d) myopathy, compassionate-use oral administration of pyrimidine deoxynucleosides have shown preliminary evidence of safety and efficacy in survival of early onset patients and motor functions relative to historical TK2d controls. Summary: The prospects of effective therapies that improve the quality of life for patients with mitochondrial myopathy underscore the necessity for definitive diagnoses natural history studies for better understanding of the diseases.