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MedKoo Cat#: 201800 | Name: Imisopasem manganese
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Imisopasem manganese , also known as M40403, or GC4419, is a manganese-based non-peptidyl mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD), with potential antioxidant and chemo/radioprotective activities. Upon administration, 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.

Chemical Structure

Imisopasem manganese
Imisopasem manganese
CAS#218791-21-0

Theoretical Analysis

MedKoo Cat#: 201800

Name: Imisopasem manganese

CAS#: 218791-21-0

Chemical Formula: C21H35Cl2MnN5

Exact Mass: 0.0000

Molecular Weight: 483.38

Elemental Analysis: C, 52.18; H, 7.30; Cl, 14.67; Mn, 11.37; N, 14.49

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,150.00 Ready to ship
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No Data
Synonym
M40403; M 40403; M-40403; CG4419; CG 4419; CG-4419; SC72325; SC-72325; SC 72325; Imisopasem manganese
IUPAC/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')-.
InChi Key
WXEMWBBXVXHEPU-QUDNGXPYSA-L
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
SMILES Code
[H][N@]1([C@H]2[C@H]3CCCC2)CC4=[N]5C(C[N]6([H])[C@H]7CCCC[C@H]7[N@@]([Mn]861(Cl)5Cl)([H])CC[N@@]38[H])=CC=C4
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
Imisopasem manganese (M40403) is a stable non-peptidyl mimetic of manganese superoxide MnSOD.
In vitro activity:
These data along with the observed results of sperm MT-G staining lead to the hypothesis that M40403 SOD mimic could improve the functional status of sperm mitochondria and, subsequently, sperm quality. In line with this is M40403-stimulated increase of mRNA expression of the nucleus encoded subunits of both ETC components—complex I and IV, in relation to the untreated group. Considering that the expression of mitochondrial ETC proteins is related to metabolic rate and sperm quality, the physiological significance of this finding rests in the suggestion that M40403 might increase the mitochondrial energy producing potential. Besides, the data indicate that changes in spermatozoa redox state, after treatment with the SOD mimic, may affect the transcription of nuclear genes encoding mitochondrial proteins. In addition, in accordance with the hypothesized improvement in the functional status of sperm mitochondria and so, the fertilizing ability of spermatozoa by M40403 is, here detected in an increase in sperm motility, which is a crucial parameter of semen fertility. Reference: Antioxid Redox Signal. 2013 Jan 10; 18(2): 170–178. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513981/
In vivo activity:
This study next wanted to address whether the M40403 SOD-mimetic could provide beneficial effects in vivo. Pink1 and parkin mutant and control flies were raised on food dosed with varying concentrations of M40403 and climbing ability was again tested. In parallel, animals of the same genotypes were raised on standard non-drug treated food for comparison. For both Pink1 and parkin mutants M40403 treatment significantly improved climbing ability (Fig. 8). The rescue was largely in a dose dependent manner within the range analysed. However, while in parkin mutants a modest rescue was seen with the lowest dose (0.01 mm), which was not significant in Pink1 mutants, the beneficial effects were lost at the highest dose (0.1 mm), which afforded the best rescue in Pink1 mutants. Taken together these results indicate that increasing endogenous or exogenous SOD activity can be beneficial in two in vivo models of PD (Parkinson’s Disease). Reference: Hum Mol Genet. 2018 May 1; 27(9): 1618–1629. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905640/
Solvent mg/mL mM
Solubility
DMSO 5.0 10.34
DMF 3.0 6.21
Ethanol 20.0 41.38
PBS (pH 7.2) 3.0 6.21
Water 16.0 33.10
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 483.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Filograna R, Godena VK, Sanchez-Martinez A, Ferrari E, Casella L, Beltramini M, Bubacco L, Whitworth AJ, Bisaglia M. Superoxide Dismutase (SOD)-mimetic M40403 Is Protective in Cell and Fly Models of Paraquat Toxicity: IMPLICATIONS FOR PARKINSON DISEASE. J Biol Chem. 2016 Apr 22;291(17):9257-67. doi: 10.1074/jbc.M115.708057. Epub 2016 Mar 7. PMID: 26953346; PMCID: PMC4861490. 2. Otasevic V, Korac A, Vucetic M, Macanovic B, Garalejic E, Ivanovic-Burmazovic I, Filipovic MR, Buzadzic B, Stancic A, Jankovic A, Velickovic K, Golic I, Markelic M, Korac B. Is manganese (II) pentaazamacrocyclic superoxide dismutase mimic beneficial for human sperm mitochondria function and motility? Antioxid Redox Signal. 2013 Jan 10;18(2):170-8. doi: 10.1089/ars.2012.4684. Epub 2012 Jun 12. PMID: 22563824; PMCID: PMC3513981. 3. Biosa A, Sanchez-Martinez A, Filograna R, Terriente-Felix A, Alam SM, Beltramini M, Bubacco L, Bisaglia M, Whitworth AJ. Superoxide dismutating molecules rescue the toxic effects of PINK1 and parkin loss. Hum Mol Genet. 2018 May 1;27(9):1618-1629. doi: 10.1093/hmg/ddy069. PMID: 29529199; PMCID: PMC5905640. 4. Murphy CK, Fey EG, Watkins BA, Wong V, Rothstein D, Sonis ST. Efficacy of superoxide dismutase mimetic M40403 in attenuating radiation-induced oral mucositis in hamsters. Clin Cancer Res. 2008 Jul 1;14(13):4292-7. doi: 10.1158/1078-0432.CCR-07-4669. PMID: 18594012.
In vitro protocol:
1. Filograna R, Godena VK, Sanchez-Martinez A, Ferrari E, Casella L, Beltramini M, Bubacco L, Whitworth AJ, Bisaglia M. Superoxide Dismutase (SOD)-mimetic M40403 Is Protective in Cell and Fly Models of Paraquat Toxicity: IMPLICATIONS FOR PARKINSON DISEASE. J Biol Chem. 2016 Apr 22;291(17):9257-67. doi: 10.1074/jbc.M115.708057. Epub 2016 Mar 7. PMID: 26953346; PMCID: PMC4861490. 2. Otasevic V, Korac A, Vucetic M, Macanovic B, Garalejic E, Ivanovic-Burmazovic I, Filipovic MR, Buzadzic B, Stancic A, Jankovic A, Velickovic K, Golic I, Markelic M, Korac B. Is manganese (II) pentaazamacrocyclic superoxide dismutase mimic beneficial for human sperm mitochondria function and motility? Antioxid Redox Signal. 2013 Jan 10;18(2):170-8. doi: 10.1089/ars.2012.4684. Epub 2012 Jun 12. PMID: 22563824; PMCID: PMC3513981.
In vivo protocol:
1. Biosa A, Sanchez-Martinez A, Filograna R, Terriente-Felix A, Alam SM, Beltramini M, Bubacco L, Bisaglia M, Whitworth AJ. Superoxide dismutating molecules rescue the toxic effects of PINK1 and parkin loss. Hum Mol Genet. 2018 May 1;27(9):1618-1629. doi: 10.1093/hmg/ddy069. PMID: 29529199; PMCID: PMC5905640. 2. Murphy CK, Fey EG, Watkins BA, Wong V, Rothstein D, Sonis ST. Efficacy of superoxide dismutase mimetic M40403 in attenuating radiation-induced oral mucositis in hamsters. Clin Cancer Res. 2008 Jul 1;14(13):4292-7. doi: 10.1158/1078-0432.CCR-07-4669. PMID: 18594012.
 1: Thompson JS, Chu Y, Glass J, Tapp AA, Brown SA. The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation. Free Radic Res. 2010 May;44(5):529-40. PubMed PMID: 20298121. 2: Murphy CK, Fey EG, Watkins BA, Wong V, Rothstein D, Sonis ST. Efficacy of superoxide dismutase mimetic M40403 in attenuating radiation-induced oral mucositis in hamsters. Clin Cancer Res. 2008 Jul 1;14(13):4292-7. PubMed PMID: 18594012. 3: Cuzzocrea S, Mazzon E, Paola RD, Genovese T, Muià C, Caputi AP, Salvemini D. Effects of combination M40403 and dexamethasone therapy on joint disease in a rat model of collagen-induced arthritis. Arthritis Rheum. 2005 Jun;52(6):1929-40. PubMed PMID: 15934059. 4: Di Paola R, Mazzon E, Rotondo F, Dattola F, Britti D, De Majo M, Genovese T, Cuzzocrea S. Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic. Eur J Pharmacol. 2005 Jun 1;516(2):151-7. PubMed PMID: 15921679. 5: Nicotera TM, Ding D, McFadden SL, Salvemini D, Salvi R. Paraquat-induced hair cell damage and protection with the superoxide dismutase mimetic m40403. Audiol Neurootol. 2004 Nov-Dec;9(6):353-62. Epub 2004 Oct 1. PubMed PMID: 15467288. 6: Di Filippo C, Cuzzocrea S, Marfella R, Fabbroni V, Scollo G, Berrino L, Giugliano D, Rossi F, D'Amico M. M40403 prevents myocardial injury induced by acute hyperglycaemia in perfused rat heart. Eur J Pharmacol. 2004 Aug 16;497(1):65-74. PubMed PMID: 15321736. 7: Jiang F, Guo Y, Salvemini D, Dusting GJ. Superoxide dismutase mimetic M40403 improves endothelial function in apolipoprotein(E)-deficient mice. Br J Pharmacol. 2003 Jul;139(6):1127-34. PubMed PMID: 12871831; PubMed Central PMCID: PMC1573947. 8: Marzocca C, Vannacci A, Cuzzocrea S, Salvemini D, Mannaioni PF, Masini E. Effects of the SOD mimetic, M40403, on prostaglandin production in an in vivo model of ischemia and reperfusion in rat heart. Inflamm Res. 2003 Apr;52 Suppl 1:S23-4. PubMed PMID: 12755394. 9: Samlowski WE, Petersen R, Cuzzocrea S, Macarthur H, Burton D, McGregor JR, Salvemini D. A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects. Nat Med. 2003 Jun;9(6):750-5. Epub 2003 May 5. PubMed PMID: 12730689. 10: McFadden SL, Ding D, Salvemini D, Salvi RJ. M40403, a superoxide dismutase mimetic, protects cochlear hair cells from gentamicin, but not cisplatin toxicity. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):46-54. PubMed PMID: 12583992. 11: Wang C, McInnis J, West JB, Bao J, Anastasio N, Guidry JA, Ye Y, Salvemini D, Johnson KM. Blockade of phencyclidine-induced cortical apoptosis and deficits in prepulse inhibition by M40403, a superoxide dismutase mimetic. J Pharmacol Exp Ther. 2003 Jan;304(1):266-71. PubMed PMID: 12490600. 12: Masini E, Cuzzocrea S, Mazzon E, Marzocca C, Mannaioni PF, Salvemini D. Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo. Br J Pharmacol. 2002 Jul;136(6):905-17. Erratum in: Br J Pharmacol. 2002 Dec;137(8):1387. PubMed PMID: 12110615; PubMed Central PMCID: PMC1573411. 13: Salvemini D, Mazzon E, Dugo L, Serraino I, De Sarro A, Caputi AP, Cuzzocrea S. Amelioration of joint disease in a rat model of collagen-induced arthritis by M40403, a superoxide dismutase mimetic. Arthritis Rheum. 2001 Dec;44(12):2909-21. PubMed PMID: 11762952. 14: Cuzzocrea S, Mazzon E, Dugo L, Caputi AP, Riley DP, Salvemini D. Protective effects of M40403, a superoxide dismutase mimetic, in a rodent model of colitis. Eur J Pharmacol. 2001 Nov 30;432(1):79-89. PubMed PMID: 11734191. 15: Coppey LJ, Gellett JS, Davidson EP, Dunlap JA, Lund DD, Salvemini D, Yorek MA. Effect of M40403 treatment of diabetic rats on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve. Br J Pharmacol. 2001 Sep;134(1):21-9. PubMed PMID: 11522593; PubMed Central PMCID: PMC1572916. 16: Salvemini D, Mazzon E, Dugo L, Riley DP, Serraino I, Caputi AP, Cuzzocrea S. Pharmacological manipulation of the inflammatory cascade by the superoxide dismutase mimetic, M40403. Br J Pharmacol. 2001 Feb;132(4):815-27. PubMed PMID: 11181422; PubMed Central PMCID: PMC1572614.  
Yim SK, Kim KM, Lee CH, Song EK, Lee SO, Kim SW, Kim IH, Kim SH, Seo SY, Lee ST. 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. doi: 10.21873/invivo.12401. PMID: 33910826.