Cysteamine targets lysosomes and cystine. It is transported into lysosomes where it reacts with cystine, forming cysteine and cysteine-cysteamine mixed disulfide. This reaction helps to deplete cystine accumulation in lysosomes, which is the basis for its use in treating cystinosis. It also has antioxidant properties.

Cysteamine is a thiol-containing compound that can act as an antioxidant. It is readily transported into lysosomes where it reacts with cystine. It has been used experimentally as a radioprotective agent and as an antidote to acetaminophen. It can produce acute and chronic duodenal ulcers in rats.

Cysteamine is used as an antidote to acetaminophen and as a radioprotective agent. It is also used in the treatment of cystinosis. It has been studied for its potential in various other conditions, including neurodegenerative diseases.

Cysteamine is evaluated in cell-free assays for its ability to react with cystine. However, specific enzymatic or receptor binding assays are not well-documented. Its antioxidant activity can be assessed using biochemical assays.

Cysteamine is assessed in cell-based assays to study its effects on cystine accumulation in lysosomes. Cells are treated with Cysteamine, and cystine levels are measured. Its antioxidant effects are also studied in cell culture models of oxidative stress.

Cysteamine is administered in animal models to evaluate its effects as a radioprotective agent and as an antidote to acetaminophen. It has been studied in models of cystinosis. However, specific animal study protocols are not extensively documented.

Absorption, Distribution and Excretion
Orally administered cysteine is absorbed from the gastrointestinal tract, reaching peak plasma concentrations in approximately 1.4 hours, though the exact time varies depending on the formulation type (sustained-release or immediate-release). A pharmacokinetic study in adult patients with cystic fibrosis showed a Cmax of 2.86 mg/L. Peak plasma concentrations after ophthalmic drop administration are unknown but are likely significantly lower than those after oral administration. Based on prescribing information, the AUC_{0-12 h} for sustained-release oral tablets is 99.26 ± 44.2 μmolh/L, and the Cmax is 27.70 ± 14.99 μmol/L. The AUC_0-12 for immediate-release tablets is 192.00 ± 75.62 μmolh/L, and the Cmax is 37.72 ± 12.10 μmol/L. According to a pharmacokinetic study, the volume of distribution of cysteine is approximately 129 L. Prescription information shows that the volume of distribution (VOD) of the sustained-release formulation is 382 L, and that of the immediate-release formulation is 198 L. Cysteine is known to cross the blood-brain barrier. The plasma clearance of cysteine is approximately 1.2–1.4 L/min. One reference mentions a clearance of 89.9 L/h in patients with cystic fibrosis. Cysteine has low binding to plasma proteins. It is currently unknown whether cysteine is excreted into breast milk. In a patient with cystinosis, oral cysteine was rapidly absorbed, reaching a peak plasma cysteine concentration of 56 μM one hour after administration. After 1.8 hours, the plasma cysteine concentration decreased to half of its peak value. In a single-dose, open-label, steady-state study, 11 patients with cystinosis received cysteine tartrate at a standard dose. Blood samples were collected and plasma cysteine and leukocyte cystine levels were analyzed. Pharmacokinetic and pharmacodynamic parameters were estimated using a correlated pharmacokinetic-pharmacodynamic model via NONMEM analysis. Cysteine was rapidly cleared from plasma (mean clearance/blood flow rate = 32.3 mL min⁻¹ kg⁻¹, range = 17.3–52.2) and widely distributed (mean steady-state volume of distribution/blood flow rate = 15.1 L, range = 2.7–32.3 L), with a mean time to peak concentration (Tmax) of 1.4 hours. Leukocyte cystine levels were significantly reduced after administration compared to pre- and post-administration levels (mean reduction of approximately 47%). A counterclockwise lag was observed in all patients, indicating a lag between drug concentration and effect (mean lag time = 0.44 hours, range = 0.22–0.92 hours). These results suggest that while cysteine is rapidly cleared from plasma, administration every 6 hours is sufficient to maintain leukocyte cystine levels below the target value of 1 nmol cystine/mg protein. Cysteine tartrate/
Cysteine (β-mercaptoethylamine, MEA) is currently used to treat children with nephrotic cystinosis. This study compared the ability of MEA and cysteine phosphate (MEAP, a thiophosphate ester with a better taste and smell than MEA) to increase plasma MEA levels and reduce leukocyte cystine levels. The study included six children aged 2 to 10 years with nephrotic cystinosis. Plasma cysteine levels were measured at different time points within 6 hours after administration of an equimolar dose of MEA or MEAP. MEA was measured using the sodium borohydride reduction method, followed by high-performance liquid chromatography (HPLC) separation and electrochemical detection. Leukocyte cystine levels were measured before administration and at 1 and 6 hours after administration. Peak plasma MEA levels were reached 30 minutes to 1 hour after administration, with no significant difference in peak plasma MEA levels between MEA (48.6 ± 10.7, mean ± standard deviation) and MEAP (54.1 ± 20.2) after administration. Significant plasma MEA concentrations were observed within 15 minutes of oral administration, indicating rapid absorption. Vomitus analysis showed that the phosphate groups of MEAP were hydrolyzed in the stomach. The percentage decrease in leukocyte cystine levels after MEA administration (61.9%) was not significantly different from the percentage decrease observed after MEAP administration (65.3%). MEA and MEAP appear to have similar efficacy in clearing cystine.

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Metabolic/Metabolites
Literature on cysteamine metabolism is limited. This drug undergoes significant first-pass metabolism.

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Biological Half-Life
The half-life of cysteamine is approximately 3.7 hours.
Cysteamine has a molecular weight of 77.15 and a molecular formula of C2H7NS. It has a CAS number of 60-23-1. The compound is soluble in water and alcohol. It is unstable in air and is typically used as a salt.

Hepatotoxicity
In pre-registration studies, a small number of patients on long-term cysteine treatment experienced elevated serum ALT levels, but the background incidence of elevated serum enzymes in this population is high and not clearly defined in open-label studies. Elevated enzymes have been reported to be more pronounced during high-dose cysteine treatment and to recur after re-administration. These abnormalities are usually asymptomatic and can be rapidly reversed by dose adjustment. Furthermore, patients with cystinosis appear to be at risk for nodular regenerative hyperplasia and non-cirrhotic portal hypertension. The role of long-term cysteine treatment in these liver complications is unclear. Despite the limited use of cysteine, there have been no reported cases of clinically significant acute liver injury with jaundice. Probability Score: D [HD] (High-dose administration may lead to liver injury). Protein Binding Cysteine has a plasma protein binding rate of 52%, primarily bound to albumin. Non-human Toxicity Oral LD50 in mice: 625 mg/kg Intraperitoneal LD50 in mice: 250 mg/kg
No detailed toxicity data is available for Cysteamine beyond its known uses. The compound is for research use and therapeutic applications. It is generally well-tolerated but can cause gastrointestinal side effects.

Therapeutic Uses
Cysteine is indicated for the treatment of nephrotic cystinosis in children and adults. /US Product Label Includes/ Nephrotic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, which encodes the cystine transporter on the lysosomal membrane. Patients have intracellular cystine stores that are 50-100 times higher than normal, accompanied by tubular and glomerular disease, growth retardation, photophobia, and other systemic complications, including myopathy and dysphagia. We evaluated the swallowing function of 101 patients with nephrotic cystinosis who were most recently admitted to the National Institutes of Health Clinical Center between 1987 and 2004 using video fluoroscopy and ultrasound. These patients were between 6 and 45 years of age; more than half of them complained of dysphagia. Barium meal examination revealed oral phase dysphagia in 24% of patients, pharyngeal phase dysphagia in 51% of patients, and esophageal phase dysphagia in 73% of patients. The incidence of swallowing dysfunction at each stage increased with age. Swallowing severity scores (an indicator of dysfunction observed during barium swallow examination) and oral muscle comprehensive scores (reflecting vocal strength, orofacial movement, and tongue and lip function) both increased with the number of years the patient had not received cysteine (the preferred cystine clearer for cystinosis) treatment (i.e., disease worsening). Severity scores decreased with increasing years of cysteine treatment. Swallowing severity scores were positively correlated with the severity of muscle disease but not with the presence or absence of the 57 kb CTNS gene deletion commonly seen in patients with nephrotic cystinosis. We conclude that swallowing dysfunction in patients with cystinosis carries a risk of fatal aspiration, is associated with muscle atrophy, and, based on cross-sectional data, its incidence increases with age and the number of years without cysteine treatment. For pre- and post-transplant cystinosis patients, cysteine clearance therapy with cysteine should be considered as the preferred treatment option.
/EXPL THER/ N-acetylcysteine (NAC) primarily protects the liver from acetaminophen-induced toxicity by providing a precursor for the glutathione synthase pathway, while cysteamine has been shown to alter the formation of cytochrome P-450-dependent acetaminophen toxic metabolites. In mice, after injection of acetaminophen (500 mg/kg), serum alanine aminotransferase (ALT) levels increased to 273.0 ± 37.5 U/mL at 12 hours and 555.8 ± 193.4 U/mL at 24 hours. Administration of cysteamine (100 mg/kg) or N-acetylcysteine (NAC, 500 mg/kg) significantly reduced serum ALT activity (p < 0.001). Reducing the dose of NAC or cysteine by 50% significantly decreased their hepatoprotective effect. However, in cases of acetaminophen overdose, combined administration of lower doses of NAC (250 mg/kg) and cysteine (50 mg/kg) prevented an increase in serum ALT activity (39.2 ± 1.17 and 32.5 ± 5.63 U/mL at 12 and 24 hours post-injection, respectively, p < 0.001) and maintained normal liver histology in mice. Lower doses of NAC (500 mg/kg), cysteine (100 mg/kg), or a combination of both did not alter the half-life or peak concentration of acetaminophen. Hepatic microsomal aryl hydroxylase activity measured 24 hours after administration showed no significant difference between the treatment group and the control group receiving only saline. These results suggest that the combined use of NAC and cysteine may help prevent liver necrosis induced by toxic doses of acetaminophen. In mice, the decrease in plasma acetaminophen levels or the inhibition of cytochrome P-450 enzyme activity did not appear to be protective mechanisms when NAC, cysteine, or a combination of both were co-administered with toxic doses of acetaminophen. Although kidney disease is the most prominent feature of lysosomal storage cystinosis, corneal cystine lens formation remains a major complication, leading to photophobia, corneal erosion, and corneal lesions. Furthermore, the degree of corneal lens accumulation reflects the course and severity of the disease itself, and the cornea can be directly examined. Therefore, we employed a scoring system based on a set of corneal slit-lamp photographs with lens densities ranging from 0.00 to 3.00 to assess the degree of lens deposition in 170 patients with nephrotic cystinosis examined at the National Institutes of Health in the United States between 1976 and 2000. None of the patients had received topical cystine removal therapy at the time of assessment. In this natural history study, infants in the first year of life had absent or minimal corneal lenses, with a corneal cystine lens score (CCCS) of 0 or 0.25. However, the CCCS increased linearly with age, with all patients having visible lenses by 16 months of age, and stabilizing at approximately 3.00 in early adolescence. Longitudinal studies of representative patients supported the cross-sectional findings. Individuals carrying homozygous 57 kb deletions involving the cystinopathy gene (CTNS) experienced the same corneal lens deposition process as those without this large deletion. The amount of corneal lens deposition (CCCS) in ocular or non-nephrotic cystinopathy patients was typically about half that of age-matched nephrotic cystinopathy patients. In 10 representative patients with nephrotic cystinopathy aged 1 to 32 years, daily use of 0.55% cysteine eye drops 6 to 12 times resulted in the dissolution of corneal cystine lenses over 8 to 41 months.
During radiotherapy, achieving adequate protection requires the use of radioprotective drugs at doses close to toxicity, a significant challenge in human medicine. A promising strategy to mitigate the toxicity of these drugs is to incorporate them into biocompatible polymers. In this study, cysteine (Cy) was ionicly linked to polyoxyethylene phosphate (POEP). The study determined the radioprotective effect of this substance on E. coli B cells and its acute toxicity in male C57BL mice. Results showed that Cy immobilized in POEP exhibited significantly reduced toxicity compared to pure cyclophosphamide (Cy), while maintaining high radioprotective efficiency at half the maximum tolerated dose. In mouse models, the high radioprotective efficiency of the Cy/POEP complex was further confirmed under different polymer molecular weight characteristics, drug immobilization levels, administration times, and doses. The study found that POEP with a molecular weight of 4700 Da and containing 24% repeating units linked to Cy exhibited the highest protective potential and a sustained-release effect.

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Drug Warnings
The most common adverse reactions involve the gastrointestinal and central nervous system, especially at the beginning of treatment. Temporarily discontinuing the drug and then gradually restarting treatment may help improve tolerability.
The most common adverse reactions (>5%) include vomiting (35%), anorexia (31%), fever (22%), diarrhea (16%), somnolence (11%), and rash (7%). Other adverse reactions include: Central nervous system: somnolence; encephalopathy; headache; seizures; ataxia; confusion; tremor; ADHD; hearing loss; dizziness; nervousness. Gastrointestinal: nausea; halitosis; abdominal pain; indigestion; constipation; gastroenteritis; duodenitis; duodenal ulcer. Mental health: nervousness; abnormal thinking; depression; mood instability; hallucinations; nightmares. Other: abnormal liver function; anemia; leukopenia; dehydration; hypertension; urticaria.
Cysteine occasionally causes reversible leukopenia and abnormal liver function.
Therefore, blood cell counts and liver function tests should be monitored. Patients allergic to penicillamine may also be allergic to this drug. FDA Pregnancy Category C: Inadequate, well-controlled human studies are lacking, and animal studies have not shown any risk to the fetus or lack relevant data. Use of this drug during pregnancy may cause harm to the fetus; however, the potential benefits may outweigh the potential risks. For more complete data on cysteine warnings (11 in total), please visit the HSDB record page.

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Pharmacodynamics
Cysteine accumulation is a cause of organ damage due to cystinosis. Cysteine prevents the accumulation of cystine crystals in the body and is specifically designed to prevent kidney and eye damage. Cysteine converts cystine into a form that is easily excreted from cells, thus preventing harmful accumulation.
Cysteamine is a small molecule with a thiol group. It has a CAS number of 60-23-1. It is used as an antidote to acetaminophen and as a radioprotective agent. It is also used in the treatment of cystinosis. It is a therapeutic agent.

C2H7NS

77.14

77.029

60-23-1

156-57-0 (hydrochloride);16904-32-8 (di-hydrochloride);27761-19-9 (tartrate (1:1));3037-04-5;42954-15-4 (hydrobromide);93965-19-6 (maleate (1:1))

6058

Crystals by sublimation in vacuo
Crystals from alcohol

1.0±0.1 g/cm3

133.6±23.0 °C at 760 mmHg

95°C

34.6±22.6 °C

8.4±0.2 mmHg at 25°C

1.486

0.03

2

2

1

4

10

0

S([H])C([H])([H])C([H])([H])N([H])[H]

UFULAYFCSOUIOV-UHFFFAOYSA-N

InChI=1S/C2H7NS/c3-1-2-4/h4H,1-3H2

2-aminoethanethiol

L 1573; Cystagon; Cysteamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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