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| 50mg |
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Imisopasem manganese (M40403, GC4419) is a novel, potent, manganese-based and non-peptidyl mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD), with potential antioxidant and chemo/radioprotective activities. Imisopasem manganese mimics the activity of MnSOD and scavenges reactive oxygen species (ROS), such as superoxide anion, which prevents oxygen free radical damage to macromolecules such as DNA. This reduces ROS-mediated lipid peroxidation, prevents apoptosis and protects against oxygen free radical-induced toxicity in normal tissues.
| ln Vitro |
Manganese imisoparsonin is a synthetic manganese small molecule that contains a superoxide dismutase mimetic (SODm) that eliminates superoxide anions without interfering with other active ingredients including nitric oxide (NO) and peroxynitrite (ONOO-) that are known to be involved in inflammatory responses [1].
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| ln Vivo |
A small chemical superoxide dismutase mimic called imisomersonin has demonstrated effectiveness in animal model illness situations where superoxide anion is believed to be important. The inflammatory response in rats following intrapleural injection of carrageenan is inhibited by manganese imisoparsonin. All inflammatory indicators were reduced by imisopasem manganese, with the exception of NOx, PGE2, and IL-10, which did not decrease [1]. Imisopasem manganese pretreatment led to a considerable restoration of lymphoid and hematopoietic tissue in the large intestine (particularly the small intestine) and decreased cell death. Imisoparsonite has the potential to be a novel radioprotective agent that can effectively lessen tissue damage brought on by traumatic brain injury [2].
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| Animal Protocol |
Carrageenan-Induced Pleurisy Model:** Male Sprague-Dawley rats (300-350 g) were anesthetized with isoflurane. A skin incision was made at the left sixth intercostal space, and the underlying muscle was dissected. Saline (0.2 ml) or 1% λ-carrageenan in saline (0.2 ml) was injected into the pleural cavity. The incision was closed, and animals were allowed to recover. M40403 (5, 10, or 20 mg/kg) or vehicle (26 mM sodium bicarbonate buffer, pH 8.1-8.3) was injected intraperitoneally 15 minutes before carrageenan. At 4 hours after carrageenan injection, animals were euthanized with CO₂ [1].
* **Exudate Collection and Analysis:** The chest was opened, and the pleural cavity was rinsed with 2 ml of saline containing heparin (5 U/ml) and indomethacin (10 μg/ml). Exudate and washing solution were removed by aspiration, and total volume was measured. Exudate volume was calculated by subtracting the 2 ml injected volume. Leukocytes in the exudate were suspended in PBS and counted using a Burker's chamber after Trypan Blue staining. Cytokines (TNFα, IL-1β, IL-6, IL-10) and PGE₂ were measured in exudates by ELISA. Nitrite/nitrate levels were measured using the Griess reaction [1]. * **Tissue Collection and Analysis:** Lung tissues were collected at 4 hours after carrageenan injection. For histology, tissues were fixed in 10% buffered formaldehyde, embedded in paraffin, sectioned (7 μm), and stained with trichromic Van Gieson. For MPO and MDA assays, tissues were homogenized and processed as described. For immunohistochemistry, 7 μm cryostat sections were permeabilized with acetone, rehydrated in PBS, and incubated overnight with primary antibodies against ICAM-1, P-selectin, nitrotyrosine, or PARS. Sections were then incubated with appropriate secondary antibodies and observed under a confocal microscope [1]. |
| References |
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| Additional Infomation |
M40403 is a low molecular weight synthetic manganese-based superoxide dismutase mimic (SODm) that selectively scavenges superoxide anions. Imidazole persemam manganese is a manganese-based non-peptide compound that mimics human mitochondrial manganese superoxide dismutase (MnSOD) and possesses potential antioxidant and chemical/radioprotective activities. After administration, imidazole persemam manganese mimics the activity of MnSOD, scavenging reactive oxygen species (ROS), such as superoxide anions, thereby preventing damage to macromolecules such as DNA by oxygen free radicals. This can reduce ROS-mediated lipid peroxidation, prevent apoptosis, and protect normal tissues from toxic damage caused by oxygen free radicals. Drug Indications: For the treatment of pain and potentially for the treatment of various cancers. Mechanism of Action: M40403 is a lead drug candidate in the unique class of superoxide dismutase (SOD) mimics. These stable, low-molecular-weight compounds mimic the function of superoxide dismutase, a naturally occurring enzyme designed to scavenge superoxide free radicals present in various pain and inflammation-related diseases.
Pharmacodynamics M40403 treatment has a protective effect against ischemia-reperfusion-induced myocardial injury, suggesting that superoxide anions play a crucial role in reperfusion injury. |
| Molecular Formula |
C21H35CL2MNN5
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|---|---|
| Molecular Weight |
483.3802
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| Exact Mass |
482.164
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| CAS # |
218791-21-0
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| PubChem CID |
10195666
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| Appearance |
White to off-white solid powder
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| LogP |
4.77
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
29
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| Complexity |
381
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1CC[C@@H]2[C@@H](C1)NCCN[C@@H]3CCCC[C@H]3NCC4=CC=CC(=N4)CN2.[Cl-].[Cl-].[Mn+2]
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| InChi Key |
WXEMWBBXVXHEPU-XNPJUPKFSA-L
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| InChi Code |
InChI=1S/C21H35N5.2ClH.Mn/c1-3-10-20-18(8-1)22-12-13-23-19-9-2-4-11-21(19)25-15-17-7-5-6-16(26-17)14-24-20;;;/h5-7,18-25H,1-4,8-15H2;2*1H;/q;;;+2/p-2/t18-,19-,20-,21-;;;/m1.../s1
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| Chemical Name |
Manganese,
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]-,
(PB-7-11-2344'3')-.
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| Synonyms |
M40403 M 40403 M-40403 CG4419 CG 4419 CG-4419 SC72325 SC-72325 SC 72325
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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) |
H2O : ~25 mg/mL (~52.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 8.33 mg/mL (17.38 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0688 mL | 10.3438 mL | 20.6877 mL | |
| 5 mM | 0.4138 mL | 2.0688 mL | 4.1375 mL | |
| 10 mM | 0.2069 mL | 1.0344 mL | 2.0688 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00101621 | TERMINATED | Drug: M40403 | Cancer Pain |
MetaPhore Pharmaceuticals | 2004-08 | Phase 2 |
| NCT00033956 | SUSPENDED | Drug: M40403 | IL-2 Induced Hypotension | MetaPhore Pharmaceuticals | 2001-12 | Phase 1 Phase 2 |
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