Physicochemical Properties
| Molecular Formula | C2H8CLNS |
| Molecular Weight | 113.6096 |
| Exact Mass | 113.006 |
| CAS # | 156-57-0 |
| Related CAS # | Cysteamine-d4 hydrochloride;1219805-04-5 |
| PubChem CID | 9082 |
| Appearance | White to off-white solid powder |
| Density | 0.75 |
| Boiling Point | 116.4ºC at 760 mmHg |
| Melting Point | 67-71 °C |
| Flash Point | 24.2ºC |
| Vapour Pressure | 16.7mmHg at 25°C |
| LogP | 1.377 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 5 |
| Complexity | 10 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OGMADIBCHLQMIP-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C2H7NS.ClH/c3-1-2-4;/h4H,1-3H2;1H |
| Chemical Name | 2-aminoethanethiol;hydrochloride |
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
Biological Activity
| Targets | Cysteine hydrochloride (2-aminoethanethiol hydrochloride) has been demonstrated to raise intracellular glutathione levels in cystine cells, thereby restoring the cell's redox state. The rise in cystine cell acidity rate is also assumed to be the result of increased activity of the caspase 3 and protein inhibitor Cε, which can be regulated by cysteamine hydrochloride. Cysteamine HCl has antioxidant effects due to enhanced glutathione synthesis. Cysteamine hydrochloride is an efficient OH and HOCl scavenger; it also reacts with H2O2. Cysteine hydrochloride has recently enhanced the synthesis of heat shock proteins (HSPs), particularly Hsp40. Modeling of doxorubicin-induced AIDS inactivation by cysteamine hydrochloride as evaluated in HeLa cells and B16 cells Additionally, addition of cysteamine hydrochloride to doxorubicin in doxorubicin-resistant breast cancer cell lines Amines generate a considerable increase in cell death [1]. Hydrochloric acid (100 μM) can greatly raise the intracellular GSH levels of cultured mature oocytes and sleep granules that grow to the blastocyst stage [2]. |
| ln Vitro |
Cysteine hydrochloride (2-aminoethanethiol hydrochloride) has been demonstrated to raise intracellular glutathione levels in cystine cells, thereby restoring the cell's redox state. The rise in cystine cell acidity rate is also assumed to be the result of increased activity of the caspase 3 and protein inhibitor Cε, which can be regulated by cysteamine hydrochloride. Cysteamine HCl has antioxidant effects due to enhanced glutathione synthesis. Cysteamine hydrochloride is an efficient OH and HOCl scavenger; it also reacts with H2O2. Cysteine hydrochloride has recently enhanced the synthesis of heat shock proteins (HSPs), particularly Hsp40. Modeling of doxorubicin-induced AIDS inactivation by cysteamine hydrochloride as evaluated in HeLa cells and B16 cells Additionally, addition of cysteamine hydrochloride to doxorubicin in doxorubicin-resistant breast cancer cell lines Amines generate a considerable increase in cell death [1]. Hydrochloric acid (100 μM) can greatly raise the intracellular GSH levels of cultured mature oocytes and sleep granules that grow to the blastocyst stage [2]. Addition of cysteamine to astrocyte culture medium resulted in increased mitochondrial autophagy.[1] In HeLa cells and B16 mouse melanoma cells, cysteamine exerted a dose-dependent effect on enhancing doxorubicin-induced cell death, while having no effect on cell survival when used alone. In a doxorubicin-resistant breast cancer cell line, adding cysteamine to doxorubicin dramatically increased cell death. Downregulation of the Atg5 gene in HeLa cells blocked the chemo-sensitizing effect of cysteamine on doxorubicin cytotoxicity.[1] Addition of cysteamine to red blood cells infected with Plasmodium falciparum diminished parasite replication and resulted in a dose-dependent delay and reduction in total parasitemia in a subsequent mouse model.[1] Cysteamine restored glutathione redox status in cultured cystinotic proximal tubular epithelial cells.[1] Cysteamine counteracted increased apoptosis rates in cystinotic cells, which are associated with increased caspase 3 and protein kinase Cε activity.[1] |
| ln Vivo |
In a mouse model of Huntington's disease (HD) using transgenic mice expressing mutant huntingtin, intraperitoneal injection of cystamine (reduced to cysteamine in vivo) significantly decreased transglutaminase activity, improved symptoms, delayed onset of unusual behavior, ameliorated weight loss, and decreased mortality.[1] In mouse models of Parkinson's disease (PD) induced by MPTP, treatment with cysteamine (or cystamine) significantly decreased dopaminergic neuronal cell death and improved dopamine status, especially when administration started before MPTP exposure.[1] In a mouse model of schizophrenia, administration of cysteamine (150 mg/kg/day for 7 days) increased BDNF levels in the frontal cortex and improved neuronal cell survival.[1] In a mouse model of major depression, cysteamine administration significantly reduced depressive-like behaviors, associated with increased hippocampal BDNF levels.[1] In mouse malaria models (Plasmodium chabaudi AS and P. falciparum), treatment with cysteamine markedly reduced parasite burden and significantly increased animal survival.[1] Concomitant administration of cysteamine with suboptimal doses of artemisinin derivatives (artesunate or dihydroartemisinin) showed a dose-dependent synergistic effect, delaying disease onset, reducing peak parasitemia, and improving disease outcome.[1] In mice injected with B16 melanoma cells, concomitant administration of cysteamine and doxorubicin led to greater tumor shrinkage compared to doxorubicin alone.[1] Cysteamine inhibited the formation of chemically-induced gastric tumors and radiation-induced mammary tumors in animal models.[1] In a mouse model of pancreatic cancer, administration of cysteamine inhibited metastasis by decreasing the expression and activity of matrix metalloproteinases.[1] High doses of cysteamine (generally >200 mg/kg) administered to rats caused duodenal ulcers, serving as an experimental model for human duodenal ulcer pathophysiology.[1] Daily doses of 50-90 mg/kg in various animal models (sheep, chickens, pigs, carp) increased growth rates, while doses >140 mg/kg restricted growth and caused duodenal ulcers. This was associated with increased mRNA expression of IGF-I, IGF-II, IGF-I receptor, and IGF-I binding protein 3.[1] In patients with cystinosis, cysteamine therapy reduces the progression to end-stage renal disease, postpones or prevents extrarenal complications, and significantly improves growth.[1] In a phase IIa trial in children with NAFLD, enteric-coated cysteamine bitartrate significantly decreased serum ALT and AST levels.[1] In a phase I trial in Huntington's disease patients, cysteamine doses of 10-50 mg/kg/day were explored.[1] |
| Animal Protocol |
In a Huntington's disease mouse model (transgenic mice expressing mutant huntingtin), cystamine (which is reduced to cysteamine in cells) was administered via intraperitoneal injection.[1] In a Parkinson's disease mouse model (MPTP-induced), cysteamine (or cystamine) was administered, with the best effect observed when started before MPTP exposure.[1] In a schizophrenia mouse model, cysteamine was administered at 150 mg/kg/day for seven days.[1] In a major depression mouse model, cysteamine was administered, and behavioral tests (open field test, forced-swimming test, tail suspension test) were conducted.[1] In malaria mouse models (Plasmodium chabaudi AS, P. falciparum), cysteamine was administered to assess its effect on parasite burden and survival.[1] In a cancer mouse model (B16 melanoma), cysteamine was co-administered with doxorubicin to assess tumor shrinkage.[1] In rat models of duodenal ulcer induction, high doses of cysteamine (generally >200 mg/kg) were administered.[1] In growth promotion studies in various animals (sheep, broiler chickens, pigs, carp), cysteamine was administered daily at doses ranging from 50-90 mg/kg.[1] For teratogenicity studies in pregnant rats, high doses of 100 and 150 mg/kg of cysteamine were administered.[1] |
| ADME/Pharmacokinetics |
Basal plasma cysteamine in humans is usually below the detection limit (<0.1 mM). After oral ingestion of cysteamine bitartrate (approximately 15 mg/kg), peak plasma concentration (0.03-0.07 mM) is reached approximately one hour post-dose. Ingestion of cysteamine with food decreases its absorption by approximately 30%. In cystinosis patients, peak decline in white blood cell cystine levels coincides with peak plasma cysteamine levels, with a return to baseline approximately six hours later, justifying a four-times-daily dosing regimen for the immediate-release form. Enteric-coated cysteamine bitartrate (RP103), designed for release in the small intestine, leads to higher plasma levels and a higher area under the curve compared to gastric administration, allowing for twice-daily dosing.[1] Cysteamine can cross the blood-brain barrier, whereas its disulfide form, cystamine, cannot.[1] Endogenously, cysteamine is derived from coenzyme A degradation via pantetheinase and is subsequently oxidized to hypotaurine by cysteamine dioxygenase, then to taurine.[1] |
| Toxicity/Toxicokinetics |
High doses of cysteamine can generate hydrogen peroxide via oxidation in the presence of transition metals, causing oxidative stress, and can diminish glutathione peroxidase activity.[1] High doses (generally >200 mg/kg in rats) are ulcerogenic, causing duodenal ulcers through mechanisms involving increased gastric acid secretion, altered gastrin/ghrelin levels, and antiangiogenic effects.[1] Doses exceeding 140 mg/kg/day in animals restrict growth and cause duodenal ulcers.[1] In cystinosis patients, early adverse effects of cysteamine (now mitigated by dose titration) included hyperthermia, lethargy, and rash. Common current adverse effects include gastrointestinal complaints (managed with proton pump inhibitors) and disagreeable breath and sweat odor due to conversion to methanethiol and dimethyl sulfide.[1] Cysteamine treatment in cystinosis has been associated with rare cases of lupus nephritis and, at high doses, with vascular proliferative lesions on elbows, skin striae, and severe bone/muscular pain, potentially due to interference with collagen crosslinking.[1] In pregnant rats, high doses of cysteamine (100 and 150 mg/kg) increased risks of intrauterine death, growth retardation, and fetal malformations (cleft palate, kyphosis). It is classified as FDA Pregnancy Category C. It is advised to discontinue cysteamine before conception until after delivery in female cystinosis patients. Breast-feeding is discouraged due to unknown excretion into milk.[1] |
| References |
[1]. Cysteamine: an old drug with new potential. Drug Discov Today, 2013. 18(15-16): p. 785-92. [2]. Effect of cysteamine on glutathione level and developmental capacity of bovine oocyte matured in vitro. Mol Reprod Dev, 1995. 42(4): p. 432-6. |
| Additional Infomation |
Cysteamine hydrochloride is an alkanethiol. A mercaptoethylamine compound that is endogenously derived from the COENZYME A degradative pathway. The fact that cysteamine is readily transported into LYSOSOMES where it reacts with CYSTINE to form cysteine-cysteamine disulfide and CYSTEINE has led to its use in CYSTINE DEPLETING AGENTS for the treatment of CYSTINOSIS. See also: Cysteamine (has active moiety). Drug Indication Cystadrops is indicated for the treatment of corneal cystine crystal deposits in adults and children from 2 years of age with cystinosis. Treatment of corneal cystine crystal deposits in cystinosis Cysteamine hydrochloride is one of the salt forms of cysteamine (chemical formula: HSCH2CH2NH2), with 1 mg equivalent to 0.7 mg of cysteamine base. Other forms include phosphocysteamine and cysteamine bitartrate.[1] Cysteamine is an amino thiol derived endogenously from coenzyme A degradation. Its mechanisms of action are multifaceted and context/dose-dependent, including: cystine depletion in lysosomes (for cystinosis), antioxidant effects via increased glutathione, modulation of various enzyme activities (e.g., transglutaminase, caspase), and influence on gene expression (e.g., BDNF, HSPs).[1] It is the standard of care for the orphan disease cystinosis, where it depletes lysosomal cystine and improves renal and extrarenal outcomes.[1] It is under investigation for new indications including Huntington's disease, Parkinson's disease, NAFLD, malaria (as an adjunct), cancer (as a chemo-sensitizer), and neuropsychiatric disorders (e.g., schizophrenia, depression), leveraging its effects on transglutaminase, BDNF, autophagy, and oxidative stress.[1] The development of an enteric-coated formulation (RP103/RP104) has improved its pharmacokinetic profile, allowing less frequent dosing and potentially better gastrointestinal tolerance, facilitating its study in new indications.[1] Its effects are biphasic: antioxidant and potentially beneficial at lower concentrations, but pro-oxidant and toxic at higher doses, necessitating careful dose selection.[1] |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~880.20 mM) H2O : ≥ 50 mg/mL (~440.10 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (18.31 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 20.8 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: ≥ 2.08 mg/mL (18.31 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (18.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (880.20 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 8.8020 mL | 44.0102 mL | 88.0204 mL | |
| 5 mM | 1.7604 mL | 8.8020 mL | 17.6041 mL | |
| 10 mM | 0.8802 mL | 4.4010 mL | 8.8020 mL |