Imisopasem manganese (M40403)
(Synonyms: M40403; GC4403) 目录号 : GC34104
A SOD mimetic
Cas No.:218791-21-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: ≥96.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Animal experiment: |
Rats: Male Sprague-Dawley rats are used in the study. M40403 (5-20 mg kg-1), or an equivalent volume (0.3 mL) of vehicle (26 mm sodium bicarbonate buffer, pH 8.1-8.3), is injected intraperitoneally (i.p.) 15 min before carrageenan. At 4 h after the injection of carrageenan, the animals are killed by inhalation of CO2[1]. Mice: 30 mg dry powder M40403 is dissolved in 6.0 ml SBC adjusted to pH 8.3 with 1 M NaOH. This stock solution is diluted to 1.25 mg/mL in SBC. Two experimental models are tested. In one, the dose of IR is held constant at 8.5 Gy total body irradiation (TBI). The mice are injected i.p. with a single dose of 40 mg/kg, 30 mg/kg, 20 mg/kg or 10 mg/kg M40403. Thirty minutes later the mice receives 8.5 Gy total body irradiation (TBI). Control animals receives 0.1 ml of SBC buffer prior to TBI. In the other model, groups of 20 mice receives either 6.5 or 7.5 Gy TBI. One half of each group is treated with 2.0 mg/kg M40403 i.p. and the other with SBC 30 min before TBI. All are followed for survival[2]. |
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References: [1]. Salvemini D, et al. Pharmacological manipulation of the inflammatory cascade by the superoxide dismutase mimetic,M40403. Br J Pharmacol. 2001 Feb;132(4):815-27. |
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Imisopasem manganese is a nonpeptide superoxide dismutase (SOD) mimetic.1 It catalyzes dismutation of the superoxide anion with a catalytic rate constant of greater than 2 x 107 M-1s-1. Imisopasem manganese (1-10 mg/kg, i.v. bolus) reduces carrageenan-induced paw edema and inhibits increases in paw exudate levels of TNF-α, IL-1β, and lactate dehydrogenase (LDH) in rats. It inhibits increases in lung and ileum myeloperoxidase (MPO) levels, indicating reduced neutrophil infiltration, and increases in plasma malondialdehyde (MDA), TNF-α, and IL-1β levels in a rat model of ischemia-reperfusion injury and shock induced by splanchnic artery occlusion (SAO) when administered at doses of 0.1, 0.3, and 1 mg/kg.
1.Salvemini, D., Wang, Z.Q., Zweier, J.L., et al.A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in ratsScience286(5438)304-306(1999)
| Cas No. | 218791-21-0 | SDF | |
| 别名 | M40403; GC4403 | ||
| Canonical SMILES | [Cl-][Mn]1234([Cl-])([Mn+])[N]5=C6C=CC=C5C[NH]1[C@]7([H])CCCC[C@@]7([H])[NH]2CC[NH]3[C@@](CCCC8)([H])[C@]8([H])[NH]4C6 | ||
| 分子式 | C21H35Cl2Mn2N5- | 分子量 | 538.32 |
| 溶解度 | Water : 16 mg/mL (29.72 mM) | 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 | 1.8576 mL | 9.2882 mL | 18.5763 mL |
| 5 mM | 0.3715 mL | 1.8576 mL | 3.7153 mL |
| 10 mM | 0.1858 mL | 0.9288 mL | 1.8576 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。
The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation
Free Radic Res 2010 May;44(5):529-40.PMID:20298121DOI:10.3109/10715761003649578.
Over-expression of manganese superoxide dismutase (MnSOD) protects tissues from radiation. M40403 is a stable non-peptidyl mimetic of MnSOD that crosses cell membranes and is effective in reducing experimental inflammation. Male BALB/c mice were injected intraperitoneally (i.p.) and subcutaneously (s.c.) with M40403, 30 min before 6.5, 7.5 and 8.5 Gy total body irradiation (TBI). Whereas all control injected mice died after receiving 8.5 Gy TBI by day 17, 30 day survival of mice pre-treated i.p. with 40, 30, 20 or 10 mg/kg was 100%, 90%, 81% and 25%, respectively. The Dose Reduction Factor 50/30 for animals treated with 30 mg M40403 s.c. 30 min prior to TBI was 1.41. Decreased apoptosis of the large and particularly the small bowel and marked recovery of both lymphoid and hematopoietic tissues occurred in the M40403 pre-treated animals. M40403 is effective in reducing TBI-induced tissue destruction and has potential as a new radioprotective agent.
Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice
PNAS Nexus 2022 Sep 14;1(4):pgac191.PMID:36276587DOI:10.1093/pnasnexus/pgac191.
Increased oxidative stress underlies a variety of diseases, including diabetes. Here, we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multifaceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M-1 s-1, respectively, for cobinamide with the cobalt in the +2 oxidation state. Cobinamide with the cobalt in the +3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M-1 s-1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, Imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals' drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress.
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models
J Inorg Biochem 2021 Jun;219:111431.PMID:33798828DOI:10.1016/j.jinorgbio.2021.111431.
Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2'-n-butoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1,4, 7,10] tetraazacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N'-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.
Superoxide: a key player in hypertension
FASEB J 2004 Jan;18(1):94-101.PMID:14718390DOI:10.1096/fj.03-0428com.
Superoxide is increased in the vessel wall of spontaneously hypertensive rats (SHR) where, if "blocked," potentiates endothelium-dependent vasodilation. The purpose of this study was to determine the role of superoxide anion in hypertension and its interaction with nitric oxide (NO). For this purpose we used a low molecular weight synthetic superoxide dismutase mimetic (M40403), known to remove selectively superoxide anion. Baseline mean arterial pressure (MAP) was significantly elevated in the SHR compared with its normal counterpart, Wistar Kyoto (WKY). M40403 at a dose (2 mg x kg(-1) x h(-1)), which had no effect in the WKY, significantly decreased MAP in SHR rats. To determine whether superoxide anion increases MAP by inactivating NO, NO synthesis was blocked with N(G) nitro-arginine methyl ester (L-NAME, 3 mg/kg i.v.), a nonselective nitric oxide synthase inhibitor. L-NAME (3 mg/kg, i.v) blocked the anti-hypertensive effect of M40403 (2 mg/kg over 30 min). When used at a dose that yielded similar increases in MAP, norepinephrine (2.1 microg/kg) failed to alter the anti-hypertensive effects of M40403 in the SHR. To investigate whether the anti-hypertensive effect of M40403 was associated with an improvement of the alterations in vascular reactivity, a separate group of experiments was carried out ex vivo. Endothelium-dependent vasorelaxation to acetylcholine (10 nM-10 microM), an index of endothelial function, was reduced in aortic rings taken from SHR rats when compared with WKY rats. In vivo treatment with M40403 caused an improvement of the degree of the endothelial dysfunction in SHR rats. Furthermore, immunohistochemical analysis for nitrotyrosine (the product formed from the interaction of nitric oxide with superoxide) revealed a positive staining in aorta from SHR rats. The degree of staining for nitrotyrosine was markedly reduced in tissue sections obtained from SHR rats treated with M40403. Our data suggest that overt production of superoxide in SHR couples with nitric oxide, reducing its function and leading to a loss of blood vessel tone and hypertension. Another important effect appears to be at the level of endothelial cellular integrity, where by interacting with nitric oxide, superoxide anion forms peroxynitrite and subsequent endothelial cell dysfunction. By removing superoxide, M40403 restores blood pressure to near-to-normal values.
The Superoxide Dismutase Mimetic M40403, Improves 5-Fluorouracil-induced Small Intestinal Mucositis in a Mouse Model
In Vivo 2021 May-Jun;35(3):1485-1497.PMID:33910826DOI:10.21873/invivo.12401.
Background/aim: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. Materials and methods: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. Results: M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. Conclusion: M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.