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.

Physicochemical Properties

Molecular Formula	C21H35CL2MNN5
Molecular Weight	483.3802
Exact Mass	482.164
CAS #	218791-21-0
PubChem CID	10195666
Appearance	White to off-white solid powder
LogP	4.77
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	0
Heavy Atom Count	29
Complexity	381
Defined Atom Stereocenter Count	4
SMILES	C1CC[C@@H]2[C@@H](C1)NCCN[C@@H]3CCCC[C@H]3NCC4=CC=CC(=N4)CN2.[Cl-].[Cl-].[Mn+2]
InChi Key	WXEMWBBXVXHEPU-XNPJUPKFSA-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
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')-.
Synonyms	M40403 M 40403 M-40403 CG4419 CG 4419 CG-4419 SC72325 SC-72325 SC 72325
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
References	[1]. Pharmacological manipulation of the inflammatory cascade by the superoxide dismutase mimetic,M40403. Br J Pharmacol. 2001 Feb;132(4):815-27. [2]. 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.
Additional Infomation	M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Imisopasem Manganese 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. Drug Indication Intended for the treatment of pain and possibly various forms of cancer. Mechanism of Action M40403 is the lead candidate in a unique class of compounds known as superoxide dismutase (SOD) mimetics. These stable, low molecular weight compounds mimic the effect of superoxide dismutase, a naturally occurring enzyme designed to destroy superoxide free radicals present in various diseases associated with pain and inflammation. Pharmacodynamics M40403 treatment exerts a protective effect against ischaemia-reperfusion-induced myocardial injury, supporting a key role for superoxide anion in reperfusion injuries.

Solubility Data

Solubility (In Vitro)	H2O : ~25 mg/mL (~52.15 mM)
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.