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].

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].

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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]

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]

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]

Human baseline plasma cysteamine concentrations are typically below the detection limit (<0.1 mM). After oral administration of cysteamine tartrate (approximately 15 mg/kg), peak plasma concentrations (0.03–0.07 mM) are reached approximately 1 hour after administration. Co-administration with food reduces cysteamine absorption by approximately 30%. In patients with cystinosis, the peak decrease in leukocyte cystine levels coincides with the peak of plasma cysteamine concentrations and returns to baseline levels after approximately 6 hours, thus immediate-release formulations can be taken four times daily. Enteric-coated cysteamine tartrate (RP103) is designed for release in the small intestine, resulting in higher plasma concentrations and a larger area under the curve compared to intragastric administration, thus allowing for twice-daily dosing. [1]
Cysteamine
can cross the blood-brain barrier, while its disulfide form, cystamine, cannot. [1]
Endogenous cysteamine originates from coenzyme A, which is degraded by pantothenic acid thioethylaminease, then oxidized by Cysteamine dioxygenase to taurine, and then further oxidized to taurine. [1]

High doses of Cysteamine can generate hydrogen peroxide through oxidation in the presence of transition metals, leading to oxidative stress and reducing glutathione peroxidase activity. [1] High doses (typically >200 mg/kg in rats) are ulcerative and can cause duodenal ulcers through mechanisms such as increased gastric acid secretion, altered gastrin/ghrelin levels, and anti-angiogenic effects. [1] Daily doses exceeding 140 mg/kg in animals can restrict growth and cause duodenal ulcers. [1] Early adverse reactions to Cysteamine in patients with cystinosis (now mitigated by dose titration) include high fever, somnolence, and rash. Common adverse reactions include gastrointestinal discomfort (which can be treated with proton pump inhibitors) and unpleasant halitosis and body odor due to conversion to methanethiol and dimethyl sulfides. [1]
Cysteamine treatment for cystinosis has been associated with rare cases of lupus nephritis, and high doses have also led to vascular lesions in the elbow, stretch marks on the skin, and severe bone/muscle pain, possibly due to interference with collagen cross-linking. [1]
In pregnant rats, high doses of Cysteamine (100 and 150 mg/kg) increased the risk of intrauterine death, growth retardation, and fetal malformations (cleft palate, kyphosis). It is classified as a pregnancy category C drug by the U.S. Food and Drug Administration (FDA).
Women with cystinosis are advised to discontinue Cysteamine before conception and after delivery. Breastfeeding is not recommended as it is unclear whether it is excreted into breast milk. [1]

[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.

Cysteamine hydrochloride is an alkylthiol.
A mercaptoethylamine compound, endogenously derived from the degradation pathway of coenzyme A. Cysteamine is readily transported to lysosomes and reacts with cystine in lysosomes to form Cysteamine-cysteamine disulfide and Cysteamine, and is therefore used as a cystine scavenger to treat cystinosis.
See also: Cysteamine (with active moiety).
Drug indications
Cystadrops are indicated for the treatment of corneal cystine lens deposition in adults and children aged 2 years and older.
Treatment of corneal cystine lens deposition caused by cystinosis
Cysteamine hydrochloride is one of the salt forms of cysteamine (chemical formula: HSCH2CH2NH2), 1 mg being equivalent to 0.7 mg of cysteamine base. Other forms include cysteamine phosphate and cysteamine tartrate. [1]
Cysteamine is an aminothiol, endogenously produced by the degradation of coenzyme A. Its mechanism of action is multifaceted and depends on the specific circumstances and dosage, including: depletion of cystine in lysosomes (for the treatment of cystinosis), antioxidant effects by increasing glutathione, regulation of the activity of various enzymes (e.g., transglutaminase, caspase), and influence on gene expression (e.g., brain-derived neurotrophic factor, heat shock protein). [1] It is the standard treatment for the rare disease cystinosis, depleting cystine in lysosomes and improving renal and extrarenal outcomes. [1] New indications for it are currently being investigated, including Huntington's disease, Parkinson's disease, non-alcoholic fatty liver disease, malaria (as adjunctive therapy), cancer (as a chemosensitizer), and neuropsychiatric disorders (e.g., schizophrenia, depression), utilizing its effects on transglutaminase, brain-derived neurotrophic factor, autophagy, and oxidative stress. [1]
An enteric-coated formulation (RP103/RP104) is under development. This drug has improved pharmacokinetic properties, reducing dosing frequency and potentially increasing gastrointestinal tolerability, thus facilitating its research in new indications. [1]
Its action is biphasic: at low concentrations it has antioxidant effects, which may be beneficial; at high concentrations it has pro-oxidative effects, which may be toxic, therefore careful dose selection is necessary. [1]

C2H8CLNS

113.6096

113.006

156-57-0

Cysteamine-d4 hydrochloride;1219805-04-5

9082

White to off-white solid powder

0.75

116.4ºC at 760 mmHg

67-71 °C

24.2ºC

16.7mmHg at 25°C

1.377

3

2

1

5

10

0

OGMADIBCHLQMIP-UHFFFAOYSA-N

InChI=1S/C2H7NS.ClH/c3-1-2-4;/h4H,1-3H2;1H

2-aminoethanethiol;hydrochloride

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~880.20 mM)
H2O : ≥ 50 mg/mL (~440.10 mM)

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.

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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.

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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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)