Avasopasem manganese (GC4419; M-40419) is a potent superoxide dismutase that can quickly and specifically convert O2*- into hydrogen peroxide (H2O2), preventing the initiation of this cascade reaction. Avasopasem manganese may be utilized in the research of severe oral mucositis (SOM) and cancer.

Physicochemical Properties

Molecular Formula	C21H35CL2MNN5
Molecular Weight	483.380151987076
Exact Mass	482.164
CAS #	435327-40-5
PubChem CID	23649345
Appearance	Light yellow to brown solid powder
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	0
Heavy Atom Count	29
Complexity	384
Defined Atom Stereocenter Count	4
SMILES	[Mn+2].[Cl-].[Cl-].N1CCN[C@H]2CCCC[C@@H]2NCC2=CC=CC(CN[C@H]3CCCC[C@H]13)=N2
InChi Key	WXEMWBBXVXHEPU-NDOCQCNASA-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-;;;/m0.../s1
Chemical Name	dichloromanganese;(4S,9S,14S,19S)-3,10,13,20,26-pentazatetracyclo[20.3.1.04,9.014,19]hexacosa-1(26),22,24-triene
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 Vivo	Avasopasem manganese is a medication intended to lessen the length, incidence, and severity of radiation-induced oral mucositis as well as to disrupt the development of severe cases [1].
References	[1]. Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer [published correction appears in J Clin Oncol. 2020 Jan 20;38(3):288]. J Clin Oncol. 2019;37(34):3256-3265.
Additional Infomation	Avasopasem manganese, also known as GC4419, is a highly-selective small molecule mimetic of superoxide dismutase (SOD) being investigated for the reduction of radiation-induced severe oral mucositis. This drug has potential application for radiation-induced esophagitis and oral mucositis, in addition to being currently tested against COVID-19. Avasopasem Manganese is a mimetic of the enzyme superoxide dismutase (SOD) that may potentially be used to reduce oral mucositis and esophagitis associated with radiation therapy and chemoradiotherapy. Upon administration, avasopasem manganese may mimic native SODs and catalyze the formation of molecular oxygen and hydrogen peroxide from the burst of superoxide anion present in the irradiated tissues upon radiation and/or induced by chemotherapy. This may decrease the damage of radiation and/or chemotherapy to normal tissues. Mechanism of Action Avasopasem manganese is a superoxide dismutase mimetic that rapidly and selectively converts superoxide to hydrogen peroxide and oxygen in order to protect normal tissue from radiation therapy-induced damage. This drug is currently being investigated against oral mucositis, esophagitis, and COVID-19.

Solubility Data

Solubility (In Vitro)

DMSO: 230 mg/mL (475.82 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (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.