| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Ferroptosis pathway and SOD1. CuATSM potently inhibits ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation. It directly inhibits (phospho)lipid peroxidation, accounting for its ability to block ferroptosis. Additionally, CuATSM stabilizes SOD1 protein variants, reducing their aggregation and toxicity in models of SOD1-associated familial ALS (fALS).
|
|---|---|
| ln Vitro |
In biochemical cell-free systems, CuATSM acts as a highly potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation propagation. It shows potent inhibition of (phospho)lipid peroxidation in cell-free model membrane systems. The compound also directly interacts with SOD1 protein variants, stabilizing them against misfolding and aggregation. The mechanism of radical trapping is thought to involve its redox-active copper center, which can cycle between Cu(II) and Cu(I) states to quench peroxyl radicals.
|
| ln Vivo |
CuATSM potently inhibits ferroptotic cell death induced by ferroptosis inducers such as RSL3, erastin, or iron(II). It demonstrates EC50 values of 134 nM (RSL3), 169 nM (erastin), and 171 nM (Fe2+) in N27 rat mesencephalic cells. CuATSM also prevents lipid peroxidation induced by these agents at 1 uM. It protects against a broad variety of SOD1 mutations in cell culture models of SOD1-fALS. In vascular smooth muscle cells, CuATSM prevents phenotypic switching, neointimal formation, and arterial inflammation.
|
| Enzyme Assay |
Screening assays for ferroptosis inhibition typically use cell-free membrane lipid peroxidation systems. Liposomes or isolated cellular lipids are incubated with Fe2+ to induce peroxidation, and lipid hydroperoxide levels are measured using assays such as the ferric thiocyanate method or TBARS (thiobarbituric acid reactive substances) assay. CuATSM (0.1-10 uM) is added to the reaction mixture, and its ability to inhibit peroxidation is assessed by comparing hydroperoxide levels to control samples containing known ferroptosis inhibitors like liproxstatin-1.
|
| Cell Assay |
N27 rat mesencephalic cells or primary neurons are cultured in appropriate medium. Cells are treated with ferroptosis inducers such as RSL3 (0.1 uM), erastin (1 uM), or Fe2+ (as ferrous ammonium sulfate) with or without CuATSM (0.01-10 uM) for 24 hours. Cell viability is measured using assays such as MTT, CellTiter-Glo, or PI exclusion. Lipid peroxidation is assessed using C11-BODIPY 581/591 staining by flow cytometry or fluorescence microscopy. EC50 values for protection against ferroptosis are calculated.
|
| Animal Protocol |
In animal models, CuATSM improves motor function and extends survival in SOD1G93A mice, a model of familial ALS, though high doses may not be tolerated in certain backgrounds. CuATSM has repeatedly shown promise in mouse models as a therapeutic treatment for SOD1-associated ALS. Typical administration routes include oral gavage or intraperitoneal injection. Doses range from 1-30 mg/kg/day depending on the model and study design. Pharmacodynamic endpoints include motor function assessment (rotarod, grip strength), survival analysis, and histopathological evaluation of motor neuron preservation in spinal cord tissue.
|
| ADME/Pharmacokinetics |
CuATSM is orally bioavailable and crosses the blood-brain barrier. Following oral administration, the compound distributes to the central nervous system, reaching therapeutically relevant concentrations in brain and spinal cord tissue. The copper complex remains intact during absorption and distribution. Pharmacokinetic studies indicate that CuATSM is stable in circulation and accumulates in target tissues. The half-life is estimated to be several hours, supporting once-daily dosing regimens. Metabolism likely involves minimal biotransformation due to the stability of the copper complex.
|
| Toxicity/Toxicokinetics |
CuATSM demonstrates a favorable safety profile in preclinical studies, with tolerability at therapeutic doses in animal models. High doses may not be tolerated in some mouse strains, indicating a narrow therapeutic window. In clinical studies for ALS, adverse events reported have been generally mild to moderate. The most common adverse events include infusion site reactions, fatigue, and gastrointestinal disturbances. No significant organ toxicity has been reported at clinically relevant exposures. Long-term safety is being evaluated in ongoing clinical trials.
|
| References | |
| Additional Infomation |
CuATSM is currently in Phase II/III clinical trials for the treatment of amyotrophic lateral sclerosis (ALS). The mechanism of action involves both ferroptosis inhibition and SOD1 stabilization. For research use, it is a valuable tool for studying ferroptosis in neurodegenerative disease models, particularly ALS. The compound selectively accumulates in hypoxic tissues, making it also useful for tumor imaging and potential radiation therapy applications when labeled with copper isotopes. The active enantiomer is the CuII(atsm) complex; the ligand itself (H2atsm) is inactive.
|
| Molecular Formula |
C8H14CUN6S2
|
|---|---|
| Molecular Weight |
321.912958621979
|
| Exact Mass |
321.001
|
| CAS # |
68341-09-3
|
| PubChem CID |
10064708
|
| Appearance |
Light brown to brown solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
17
|
| Complexity |
310
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C/C(=N\NC(=NC)[S-])/C(=N/NC(=NC)[S-])/C.[Cu+2]
|
| InChi Key |
SBHDKYTVDCRMOE-JPAPVDFESA-L
|
| InChi Code |
InChI=1S/C8H16N6S2.Cu/c1-5(11-13-7(15)9-3)6(2)12-14-8(16)10-4;/h1-4H3,(H2,9,13,15)(H2,10,14,16);/q;+2/p-2/b11-5+,12-6+;
|
| Chemical Name |
copper;N'-methyl-N-[(E)-[(3E)-3-[(N-methyl-C-sulfidocarbonimidoyl)hydrazinylidene]butan-2-ylidene]amino]carbamimidothioate
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~2 mg/mL (~6.2 mM; with ultrasonication and warming by heating to 80°C)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.15 mg/mL (0.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (1.5 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: 0.15 mg/mL (0.47 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Suspended solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (1.5 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1065 mL | 15.5323 mL | 31.0646 mL | |
| 5 mM | 0.6213 mL | 3.1065 mL | 6.2129 mL | |
| 10 mM | 0.3106 mL | 1.5532 mL | 3.1065 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
