Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C4H6O6.C2H7NS.H2O |
| Molecular Weight | 245.251 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.NCCS.O[C@H]([C@@H](O)C(O)=O)C(O)=O
InChI
InChIKey=FPOOGHFVXKEZBQ-OLXYHTOASA-N
InChI=1S/C4H6O6.C2H7NS.H2O/c5-1(3(7)8)2(6)4(9)10;3-1-2-4;/h1-2,5-6H,(H,7,8)(H,9,10);4H,1-3H2;1H2/t1-,2-;;/m1../s1
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/6131501 | https://www.ncbi.nlm.nih.gov/pubmed/6124307 | https://www.ncbi.nlm.nih.gov/pubmed/15675041 | https://www.ncbi.nlm.nih.gov/pubmed/28384851
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/6131501 | https://www.ncbi.nlm.nih.gov/pubmed/6124307 | https://www.ncbi.nlm.nih.gov/pubmed/15675041 | https://www.ncbi.nlm.nih.gov/pubmed/28384851
Cysteamine (trade name CYSTAGON) is a cystine-depleting agent indicated for the treatment of corneal cystine crystal accumulation in patients with cystinosis. Cystinosis is an autosomal recessive inborn error of metabolism in which the transport of cystine out of lysosomes is abnormal; in the nephropathic form, accumulation of cystine and formation of crystals damage various organs, especially the kidney, leading to renal tubular Fanconi Syndrome and progressive glomerular failure, with end-stage renal failure by the end of the first decade of life. In four studies of cystinosis patients before cysteamine was available, renal death (need for transplant or dialysis) occurred at the median age of fewer than 10 years. Patients with cystinosis also experience growth failure, rickets, and photophobia due to cystine deposits in the cornea. With time most organs are damaged, including the retina, muscles and central nervous system. Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P21980 Gene ID: 7052.0 Gene Symbol: TGM2 Target Organism: Homo sapiens (Human) |
178.0 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CYSTAGON Approved UsePROCYSBI is indicated for the treatment of nephropathic cystinosis in adult and pediatric patients 2 years of age and older. PROCYSBI is a cystine-depleting agent indicated for the treatment of nephropathic cystinosis in adult and pediatric patients 2 years of age and older. (1) Launch Date1994 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.7 mg/L |
404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
|
37.72 μM |
450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
351 mg × min/L |
404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
|
96 μM × h |
450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
90 min |
404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
48% |
404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
|
48% |
450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered: |
CYSTEAMINE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
0.44 % 1 times / day multiple, ophthalmic Recommended Dose: 0.44 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.44 %, 1 times / day Sources: Page: 98 EI0109S |
unhealthy, 13.4 (5.9-27.8) n = 20 Health Status: unhealthy Condition: cystinosis Age Group: 13.4 (5.9-27.8) Sex: M+F Population Size: 20 Sources: Page: 98 EI0109S |
Disc. AE: Intracranial hypertension... AEs leading to discontinuation/dose reduction: Intracranial hypertension Sources: Page: 98 EI0109S |
600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: Page: RP103-05 |
healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: Page: RP103-05 |
Disc. AE: Blurred vision, Hematuria... AEs leading to discontinuation/dose reduction: Blurred vision Sources: Page: RP103-05Hematuria |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Intracranial hypertension | Disc. AE | 0.44 % 1 times / day multiple, ophthalmic Recommended Dose: 0.44 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.44 %, 1 times / day Sources: Page: 98 EI0109S |
unhealthy, 13.4 (5.9-27.8) n = 20 Health Status: unhealthy Condition: cystinosis Age Group: 13.4 (5.9-27.8) Sex: M+F Population Size: 20 Sources: Page: 98 EI0109S |
| Blurred vision | Disc. AE | 600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: Page: RP103-05 |
healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: Page: RP103-05 |
| Hematuria | Disc. AE | 600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: Page: RP103-05 |
healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: Page: RP103-05 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| inconclusive | ||||
| inconclusive | ||||
| inconclusive | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| weak [Inhibition 780 uM] | ||||
| weak [Inhibition 780 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Taurine and hypotaurine in spermatozoa and epididymal fluid of cats. | 2001 |
|
| Oxidative stress, glucose-6-phosphate dehydrogenase and the red cell. | 2001 |
|
| Threonine metabolism in isolated rat hepatocytes. | 2001 Dec |
|
| Synthesis of di- to hexasaccharide 1,2-linked beta-mannopyranan oligomers, a terminal S-linked tetrasaccharide congener and the corresponding BSA glycoconjugates. | 2001 Dec 14 |
|
| Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol substituted with two methyl groups alpha to the nitrogen. | 2001 Feb |
|
| Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat. | 2001 Jan-Dec |
|
| Susceptibility of dopamine D5 receptor targeted mice to cysteamine. | 2001 Jan-Dec |
|
| Effect of centrally administered oxytocin on gastric and duodenal ulcers in rats. | 2001 Jun |
|
| Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats. | 2001 Nov |
|
| Reductive demercuration in deprotection of trityl thioethers, trityl amines, and trityl ethers. | 2001 Nov 16 |
|
| Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs. | 2001 Nov 21 |
|
| [Oxidative metabolism of HIV-infected macrophages: the role of glutathione and a pharmacologic approach]. | 2001 Sep |
|
| Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine conjugates. | 2001 Sep 11 |
|
| Role of porphyrin sequestration in the biogenesis of iron-laden astrocytic inclusions in primary culture. | 2002 |
|
| A novel strategy for the synthesis of neoglycoconjugates from deacylated deep rough lipopolysaccharides. | 2002 |
|
| In vitro maturation and glutathione synthesis of porcine oocytes in the presence or absence of cysteamine under different oxygen tensions: role of cumulus cells. | 2002 |
|
| Interventions for paracetamol (acetaminophen) overdoses. | 2002 |
|
| Enhancement of solar inactivation of Escherichia coli by titanium dioxide photocatalytic oxidation. | 2002 |
|
| Electrochemical and spectroelectrochemical behavior of the main photodegradation product of nifedipine: the nitrosopyridine derivative. | 2002 Apr |
|
| Modulation of inflammatory paw oedema by cysteamine in the rat. | 2002 Apr |
|
| Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs. | 2002 Apr |
|
| Effect of sperm survival and CTC staining pattern on in vitro fertilization of porcine oocytes. | 2002 Apr 15 |
|
| The ability of hippocampal CA1 area for induction of long-term potentiation is persistently reduced by prior treatment with cysteamine: an in vitro study. | 2002 Aug |
|
| Differentiating the orientations of photosynthetic reaction centers on Au electrodes linked by different bifunctional reagents. | 2002 Aug |
|
| In vivo confocal microscopy of the cornea in nephropathic cystinosis. | 2002 Dec |
|
| Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease. | 2002 Dec |
|
| Lysosomal cystine storage augments apoptosis in cultured human fibroblasts and renal tubular epithelial cells. | 2002 Dec |
|
| Thiol oxidase activity of copper, zinc superoxide dismutase. | 2002 Jan 18 |
|
| A molecular CT blood pool contrast agent. | 2002 Jul |
|
| Cysteine-mediated electron transfer in syntrophic acetate oxidation by cocultures of Geobacter sulfurreducens and Wolinella succinogenes. | 2002 Jul |
|
| Cystinosis. | 2002 Jul 11 |
|
| Synthesis of (+/-)-madindolines and chemical models. Studies of chemical reactivity. | 2002 Jul 11 |
|
| Gastroprotective effect of adrenomedullin administered subcutaneously in the rat. | 2002 Jun |
|
| Cysteamine supplementation during in vitro maturation and embryo culture: a useful tool for increasing the efficiency of bovine in vitro embryo production. | 2002 Jun |
|
| Prevalence of apoptosis and inner cell allocation in bovine embryos cultured under different oxygen tensions with or without cysteine addition. | 2002 Mar 15 |
|
| Effect of glutathione synthesis stimulation during in vitro maturation of ovine oocytes on embryo development and intracellular peroxide content. | 2002 Mar 15 |
|
| Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery? | 2002 Mar 2 |
|
| Negligible urinary cysteamine loss in cystinosis patients with Fanconi syndrome. | 2002 May |
|
| Properties of selected S-nitrosothiols compared to nitrosylated WR-1065. | 2002 May |
|
| Endogenous somatostatin inhibits interaction of insulin and cholecystokinin on exocrine secretion of isolated, perfused rat pancreas. | 2002 May |
|
| Tumour targeting of humanised cross-linked divalent-Fab' antibody fragments: a clinical phase I/II study. | 2002 May 6 |
|
| Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase. | 2002 Nov 12 |
|
| Cysteamine pre-treatment reduces pentylenetetrazol-induced plasticity and epileptiform discharge in the CA1 region of rat hippocampal slices. | 2002 Nov 15 |
|
| Nephropathic cystinosis associated with cardiomyopathy: a 27-year clinical follow-up. | 2002 Nov 9 |
|
| Follow-up and treatment of adults with cystinosis in the Netherlands. | 2002 Oct |
|
| Possible mechanism for involvement of cysteine in aroma production in wine. | 2002 Oct 9 |
|
| Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. | 2002 Sep |
|
| Identification and quantitation of key aroma compounds formed in Maillard-type reactions of fructose with cysteamine or isothiaproline (1,3-thiazolidine-2-carboxylic acid). | 2002 Sep 11 |
|
| Structural determination and odor characterization of N-(2-mercaptoethyl)-1,3-thiazolidine, a new intense popcorn-like-smelling odorant. | 2002 Sep 11 |
|
| Electric potential control of DNA immobilization on gold electrode. | 2003 Jan |
Sample Use Guides
The recommended maintenance dose of 1.30 grams/m2/day. Patients over age 12 and over 110 pounds should receive 2.0 grams/day given in four divided doses as a starting maintenance dose. This dose should be reached after 4 to 6 weeks of incremental dosage increases as stated above. The dose should be raised if the leukocyte cystine level remains > 2 nmol/1⁄2 cystine/mg/protein.
Route of Administration:
Oral
Oocytes were obtained from 4-6 weeks old Naval Medical Research Institute (NMRI) female mice, 48 hours after stimulation with Intraperitoneal (IP) injection of 10 IU Pregnant Mare Serum Gonadotropin (PMSG). Germinal Vesicle (GV) oocyte with and without cumulus cells were isolated from ovaries and cultured in Tissue Culture Medium (TCM) 199 with availability of 100 μM of CYS (Cysteamine). After 24 hours, mature oocyte in metaphase II (MII) were fertilized with sperm in In vitro Fertilization (IVF) medium (T6) and evaluated for fetal development into blastocyst. CYS could significantly (p<0.05) increase the rate of IVM and oocyte evolution, and embryo formation in medium culture.
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1523606-58-7
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300000040038
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75W7QP2VF6
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PARENT (SALT/SOLVATE)
SALT/SOLVATE (SALT/SOLVATE)
SUBSTANCE RECORD
