| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Superoxide anion radical (O2•-); Reactive Oxygen Species (ROS). Avasopasem manganese acts as a catalytic scavenger of superoxide. It mimics the activity of human superoxide dismutase enzymes (SOD1, SOD2, SOD3) by facilitating the dismutation of O2•- to H2O2 and O2. It does not interact with other ROS (e.g., H2O2, •OH) directly. By reducing superoxide levels, it prevents the formation of peroxynitrite (ONOO-, a potent nitrosylating agent) and downstream oxidative damage. It is specific for superoxide and is not a general antioxidant.
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| ln Vitro |
In vitro, Avasopasem manganese (GC-4419) demonstrates potent SOD mimetic activity with a rate constant for O2•- dismutation approaching that of native SOD enzymes (k ~ 10⁷-10⁸ M-¹s-¹). It protects cultured cells (e.g., fibroblasts, epithelial cells) from radiation-induced cell death and DNA damage. It reduces intracellular superoxide levels measured by dihydroethidium (DHE) fluorescence. It inhibits the formation of nitrotyrosine adducts, a marker of peroxynitrite-mediated damage. It also reduces inflammatory cytokine production (IL-6, TNF-alpha) in activated macrophages. It has a long half-life in media.
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| 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].
In vivo, Avasopasem manganese (GC-4419) provides significant protection against radiation-induced toxicity without protecting tumors. In rodent models, it reduces the incidence and severity of radiation-induced oral mucositis, esophagitis, and dermatitis. It is effective when administered 15-60 minutes before irradiation. It also protects against ischemia-reperfusion injury in heart, brain, and kidney models. It reduces oxidative stress markers (MDA, 8-OHdG) in plasma and tissues. It has shown efficacy in reducing inflammation in models of pancreatitis, colitis, and arthritis. It is an effective radioprotector. |
| Enzyme Assay |
Superoxide Dismutase (SOD) activity assay (Cytochrome c reduction): Prepare a reaction mix containing 50 mM potassium phosphate (pH 7.8), 0.1 mM EDTA, 50 uM xanthine, and 10 uM cytochrome c. Add xanthine oxidase (XO) to generate O2•-. Add Avasopasem manganese (0.1-100 nM). Monitor the reduction of cytochrome c at 550 nm (ε = 21.1 mM-¹cm-¹). The compound will inhibit cytochrome c reduction (as it removes O2•-), and the IC₅0 can be calculated. Alternatively, use a water-soluble tetrazolium (WST-1) kit which uses a colorimetric reaction.
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| Cell Assay |
For radioprotection assays, culture cells (e.g., V79 fibroblasts, HaCaT keratinocytes). Pre-treat with Avasopasem manganese (1-100 uM) for 1 hour. Irradiate cells with X-rays (2-10 Gy). After 24-72 hours, measure cell viability via clonogenic survival assay or MTT. Determine the dose reduction factor (DRF). Also measure apoptosis (caspase-3/7) and DNA damage (gamma-H2AX foci). The compound should increase survival and reduce DNA damage in a concentration-dependent manner. CellTox Green assay can be used to measure cytotoxicity. Study the protective effect.
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| Animal Protocol |
Radiation-induced oral mucositis model: Male hamsters or mice receive a single dose of ionizing radiation (e.g., 40 Gy) targeted to the cheek pouch or tongue. Avasopasem manganese (GC-4419) is administered intraperitoneally (5-50 mg/kg) 15-60 minutes before irradiation. Assess mucositis severity daily for 14-28 days using a clinical scoring scale. Measure histopathological damage, inflammatory cell infiltration (myeloperoxidase assay), and oxidative stress markers. For tumor models (subcutaneous xenografts), co-administer radiation (tumor dose) and GC-4419 to confirm tumor protection is not compromised. GC-4419 protects normal tissue but not tumors.
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| ADME/Pharmacokinetics |
Avasopasem manganese (GC-4419): Molecular formula C34H3₆MnN₉O₈ (typical for Mn porphyrin). Molecular weight: Approximately 753.65 g/mol. Appearance: Dark green/blue solid. Solubility: Soluble in water (≥10 mg/mL) and DMSO. Storage: Store powder at -20degC, protected from light. In solution, store at -80degC for up to 6 months. It is stable and non-hygroscopic. Pharmacokinetics: In rodents, plasma half-life is several hours (longer than native SOD). It distributes to mucosal tissues effectively. It is well-absorbed orally (investigational). It is not metabolized quickly.
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| Toxicity/Toxicokinetics |
Avasopasem manganese is well-tolerated in preclinical models. No significant systemic toxicity has been observed at therapeutic doses (5-50 mg/kg). Phase I/II clinical trials in humans show it is safe. Unlike some metalloporphyrins, it does not exhibit pro-oxidant activity. It does not cause significant hematological or biochemical abnormalities. It is not a general antioxidant, only a SOD mimetic. This specific mechanism reduces the risk of interfering with necessary ROS signaling. Standard laboratory safety precautions should be followed. Not approved for human use outside clinical trials (currently in Phase III for oral mucositis). Consult SDS.
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| References | |
| Additional Infomation |
Avasopasem manganese (also known as GC4419) is a highly selective small-molecule superoxide dismutase (SOD) mimic and is currently being investigated for its efficacy in alleviating severe radiation-induced oral mucositis. In addition to ongoing clinical trials for COVID-19, this drug also has potential applications in treating radiation-induced esophagitis and oral mucositis. Avasopasem manganese is a superoxide dismutase (SOD) mimic and may be used to alleviate radiation- and chemoradiotherapy-associated oral mucositis and esophagitis. After administration, avasopasem manganese mimics natural SOD, catalyzing a superoxide anion burst in radiation- and/or chemotherapy-induced irradiated tissues to generate molecular oxygen and hydrogen peroxide. This may mitigate damage to normal tissues caused by radiation and/or chemotherapy.
Mechanism of Action Avasopasem manganese is a superoxide dismutase mimic that rapidly and selectively converts superoxide into hydrogen peroxide and oxygen, thereby protecting normal tissues from radiation-induced damage. Currently, this drug is being investigated for its use in treating stomatitis, esophagitis, and COVID-19. Avasopasem manganese is a leading drug candidate for radiation-induced toxicity (severe oral mucositis). It has received Fast Track and Breakthrough Therapy designation from the FDA for this indication. It is also being studied for pancreatitis and for reducing toxicity from chemotherapy. It is distinct from other antioxidants because it is catalytic (not stoichiometric) and specific for superoxide. It does not require recharging. It is also known as GC-4419. It is a powerful research tool and a therapeutic candidate. It is a controlled substance for pharmaceutical research. Keep frozen at -20degC for long-term storage. Not for human consumption outside of clinical trials. |
| Molecular Formula |
C21H35CL2MNN5
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|---|---|
| Molecular Weight |
483.380151987076
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| Exact Mass |
482.164
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| CAS # |
435327-40-5
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| PubChem CID |
23649345
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| Appearance |
Light yellow to brown solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
29
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| Complexity |
384
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[Mn+2].[Cl-].[Cl-].N1CCN[C@H]2CCCC[C@@H]2NCC2=CC=CC(CN[C@H]3CCCC[C@H]13)=N2
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| InChi Key |
WXEMWBBXVXHEPU-NDOCQCNASA-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-;;;/m0.../s1
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| 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
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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) |
DMSO: 230 mg/mL (475.82 mM)
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| 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.
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.
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