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| Other Sizes |
| Targets |
Cystamine dihydrochloride targets transglutaminase (Tgase), an enzyme that plays a critical role in protein crosslinking by catalyzing intermolecular cross-linkages between glutamine and lysine side chains. It specifically inhibits tissue transglutaminase (TGM2) with an IC50 of approximately 2.5 mM. Additionally, cystamine inhibits caspase-3 with an IC50 of 23.6 μM. By inhibiting transglutaminase, cystamine modulates protein crosslinking and cellular processes, which is relevant to its neuroprotective effects in neurodegenerative diseases.
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| ln Vitro |
At an IC50 value of 23.6 μM, cystamine (dihydrochloride) has inhibitory effect against caspase-3 [1]. Cystamine inhibits recombinant active caspase-3 in a concentration-dependent manner (0–500 μM; 0–16 hours) [1]. Glutathione levels are markedly elevated by streptamine (250 μM; 10 hours) [1].
In vitro, cystamine attenuates cell death induced by 3-nitropropionic acid in Huntington's disease (HD) striatal cells. It functions as a transglutaminase inhibitor, reducing protein crosslinking that is implicated in the pathology of Huntington's disease. The compound also demonstrates inhibition of caspase-3 with an IC50 of 23.6 μM, suggesting additional anti-apoptotic properties. These in vitro activities support its potential as a neuroprotective agent for the treatment of neurodegenerative disorders. |
| ln Vivo |
Cystamine (dihydrochloride) (oral, i.p.; 112, 225 mg/kg) reduces Tgase activity and GGEL levels, reduces behavioral and neuropathological severity, and prolongs survival in R6/2 transgenic HD mice [ 2].
In vivo, cystamine has been shown to extend survival and decrease abnormal movements in transgenic mouse models of Huntington's disease. When administered intraperitoneally, cystamine enters the brain where it inhibits transglutaminase activity. Treatment initiated after the appearance of abnormal movements extended survival, reduced associated tremor and abnormal movements, and ameliorated weight loss in these models. These findings demonstrate the in vivo neuroprotective effects of cystamine and support its potential as a therapeutic agent for Huntington's disease. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for cystamine typically measures its ability to inhibit transglutaminase (TGM2) activity. These cell-free assays use purified enzyme and a substrate, often a peptide containing a glutamine residue, in the presence of a primary amine donor. The formation of cross-linked products is measured, and the inhibitory potency (IC50) is determined. Additionally, caspase-3 inhibition can be assessed using fluorogenic substrates in cell-free systems. These assays provide a direct measure of the compound's enzyme inhibitory activity.
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| Cell Assay |
Western Blot Analysis [1]
Cell Types: Human Neuroblastoma SH-SY5Y Cell Tested Concentrations: 250, 500 μM Incubation Duration: 0-16 h Experimental Results: Inhibition of MG132-mediated caspase-3 activation. Inhibits H2O2-mediated caspase-3 activation. Inhibits caspase-3 activity in a tTG-independent manner. In vitro cellular assays for cystamine typically use neuronal cell lines, such as striatal cells from Huntington's disease models. Cells are treated with cystamine and then exposed to a toxic insult, such as 3-nitropropionic acid. Cell death is measured using viability assays such as MTT or LDH release. The compound's ability to attenuate cell death is quantified, demonstrating its neuroprotective effects. Additionally, the effects of cystamine on protein crosslinking and apoptosis markers can be assessed in these cellular models. |
| Animal Protocol |
Animal/Disease Models: R6/2 transgenic HD mice [2]
Doses: 112, 225 mg/kg Route of Administration: intraperitonealor po (po (oral gavage)) daily Experimental Results: Dramatically prolonged survival, improved body weight and exercise capacity, and delayed neuropathological sequelae And Dramatically altered neuropathological sequelae were the levels of Tgase activity and N(Sigma)-(gamma-L-glutamyl)-L-lysine (GGEL) levels. In vivo animal studies for cystamine have been conducted using transgenic mouse models of Huntington's disease, such as the R6/2 mouse model. In these studies, cystamine is typically administered intraperitoneally. Endpoints include survival, motor function (assessed by tremor and abnormal movements), and weight loss. Brain tissue is also analyzed for transglutaminase activity and markers of neurodegeneration. These studies demonstrate the compound's ability to cross the blood-brain barrier and exert neuroprotective effects in vivo. |
| ADME/Pharmacokinetics |
Cystamine dihydrochloride is orally active and can cross the blood-brain barrier. Its oral bioavailability supports its administration as an oral therapeutic agent. However, detailed pharmacokinetic parameters such as half-life and volume of distribution are not extensively detailed in the available literature. As a disulfide, cystamine may be reduced to cysteamine in vivo, which is its active metabolite. This biotransformation is important for its pharmacological activity, as cysteamine is known to have various biological effects.
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| Toxicity/Toxicokinetics |
Cystamine dihydrochloride has been studied for its safety profile in the context of neurodegenerative diseases. As a transglutaminase inhibitor, its toxicity is likely related to its mechanism of action. However, specific toxicity data are not extensively detailed in the available literature. The compound is also a radiation-protective agent that interferes with sulfhydryl enzymes. It may protect against carbon tetrachloride liver damage. Cystamine's safety profile supports its investigation as a potential therapeutic agent for Huntington's disease.
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| References |
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| Additional Infomation |
A radiation protectant that interferes with sulfhydryl enzymes. It may also offer protection against liver damage caused by carbon tetraCloricromen.
Cystamine dihydrochloride is a research compound that has been investigated as a neuroprotective agent for neurodegenerative diseases, particularly Huntington's disease. Its mechanism of action involves inhibition of transglutaminase, which plays a role in protein crosslinking and cellular processes implicated in the pathology of Huntington's disease. The compound has been shown to extend survival and reduce abnormal movements in transgenic mouse models. It is not approved for clinical use and is intended for research purposes only. It is also utilized in apoptosis research. |
| Molecular Formula |
C4H14CL2N2S2
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|---|---|
| Molecular Weight |
225.2034
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| Exact Mass |
223.997
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| CAS # |
56-17-7
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| Related CAS # |
Cystamine;51-85-4;Cystamine-d8 (dihydrochloride）;2712126-51-5
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| PubChem CID |
5941
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| Appearance |
White to off-white solid powder
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| Density |
1.172g/cm3
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| Boiling Point |
264.8ºC at 760mmHg
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| Melting Point |
217-220 °C (dec.)(lit.)
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| LogP |
3.289
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
10
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| Complexity |
37
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YUFRRMZSSPQMOS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C4H12N2S2.2ClH/c5-1-3-7-8-4-2-6;;/h1-6H2;2*1H
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| Chemical Name |
2-(2-aminoethyldisulfanyl)ethanamine;dihydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~444.05 mM)
DMSO : ~100 mg/mL (~444.05 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.10 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 (11.10 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4405 mL | 22.2025 mL | 44.4050 mL | |
| 5 mM | 0.8881 mL | 4.4405 mL | 8.8810 mL | |
| 10 mM | 0.4440 mL | 2.2202 mL | 4.4405 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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