Identification

Name
Cysteamine
Accession Number
DB00847  (APRD00896)
Type
Small Molecule
Groups
Approved, Investigational
Description

Cysteamine is a radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate and hydrochloride salt forms are indicated for the treatment of neuropathic cystinosis in patients 6 years old and older. [PubChem]. Cysteamine is marketed under several brand names such as Cystaran™, Procysbi, and Cystagon®.

Structure
Thumb
Synonyms
  • 2-Amino-1-ethanethiol
  • 2-AMINO-ethanethiol
  • 2-Aminoethanethiol
  • beta-Aminoethanethiol
  • beta-Aminoethylthiol
  • beta-MEA
  • beta-Mercaptoethylamine
  • Cysteamine
  • MEA
  • Mercaptamina
  • Mercaptamine
  • Mercaptaminum
  • Thioethanolamine
  • β-aminoethylthiol
  • β-MEA
External IDs
L-1573
Product Ingredients
IngredientUNIICASInChI Key
Cysteamine BitartrateQO84GZ3TST27761-19-9NSKJTUFFDRENDM-UHFFFAOYSA-N
Cysteamine HydrochlorideIF1B771SVB156-57-0OGMADIBCHLQMIP-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CystagonCapsule50 mgOralOrphan Europe S.A.R.L.1997-06-23Not applicableEu
CystagonCapsule50 mg/1OralMylan Pharmaceuticals1994-08-15Not applicableUs
CystagonCapsule150 mgOralOrphan Europe S.A.R.L.1997-06-23Not applicableEu
CystagonCapsule150 mg/1OralMylan Pharmaceuticals1994-08-15Not applicableUs
CystagonCapsule50 mgOralOrphan Europe S.A.R.L.1997-06-23Not applicableEu
CystagonCapsule150 mgOralOrphan Europe S.A.R.L.1997-06-23Not applicableEu
CystaranSolution6.5 mg/mLOphthalmicSigma Tau Pharmaceuticals, Inc.2012-12-30Not applicableUs
ProcysbiCapsule, delayed release75 mgOralHorizon Pharma, Inc.Not applicableNot applicableCanada
ProcysbiCapsule, delayed release25 mgOralHorizon Pharma, Inc.Not applicableNot applicableCanada
Procysbi Delayed-releaseCapsule, delayed release pellets25 mg/1OralRaptor Therapeutics Inc.2013-04-30Not applicableUs
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ProcysbiCapsule, delayed release pellets25 mg/1OralHorizon Pharma, Inc.2013-04-30Not applicableUs
ProcysbiCapsule, delayed release pellets75 mg/1OralHorizon Pharma, Inc.2013-04-30Not applicableUs
International/Other Brands
Procysbi (Raptor Pharms)
Categories
UNII
5UX2SD1KE2
CAS number
60-23-1
Weight
Average: 77.149
Monoisotopic: 77.029919919
Chemical Formula
C2H7NS
InChI Key
UFULAYFCSOUIOV-UHFFFAOYSA-N
InChI
InChI=1S/C2H7NS/c3-1-2-4/h4H,1-3H2
IUPAC Name
2-aminoethane-1-thiol
SMILES
NCCS

Pharmacology

Indication

Given intravenously or orally to treat radiation sickness. The bitartrate salts (Cystagon® and Procysbi) have been used for the oral treatment of nephropathic cystinosis and cystinurea. The hydrochloride salt (Cystaran™) is indicated for the treatment of corneal cystine crystal accumulation in cystinosis patients.

Structured Indications
Pharmacodynamics

People born without the ability to metabolize the amino acid cystine suffer from cystinosis, a rare inherited disorder characterized by the deposition and accumulation of cystine crystals throughout the body. These crystals cause considerable damage, particularly in the kidney and eye. Kidney failure can occur by the age of 10 in untreated patients. Cysteamine prevents the accumulation of cystine crystals and is prescribed to prevent further kidney and eye damage. Cysteamine helps to convert cystine into less harmful chemical forms that can be removed from cells.

Mechanism of action

The free thiol cysteamine depletes cystinotic leukocytes and other cells of cystine, whose accumulation is considered the cause of organ damage in cystinosis. Cysteamine cleaves the disulfide bond with cystine to produce molecules that can escape the metabolic defect in cystinosis and cystinuria.

TargetActionsOrganism
UCystine
cleavage
Human
USomatostatin
binder
Human
UNeuropeptide Y receptor type 2
other/unknown
Human
Absorption

Cystagon® reaches its maximum plasma concentration in about 1.4 hours.

Volume of distribution

Cystagon® has a volume of distribution of 156 L.

Protein binding

Cysteamine has a plasma protein binding of 52% and is mostly bound to albumin.

Metabolism

The metabolism of cysteamine has not yet been determined.

Route of elimination
Not Available
Half life
Not Available
Clearance

The plasma clearance is about 1.2 L/min.

Toxicity

Symptoms of overdose may include convulsions (seizures), increased thirst and unusual tiredness or weakness.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Pantothenate and CoA BiosynthesisMetabolic
Taurine and Hypotaurine MetabolismMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AlgeldrateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Algeldrate.Approved, Experimental
AlmagateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Almagate.Experimental
AlmasilateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Almasilate.Approved, Experimental
AloglutamolThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Aloglutamol.Experimental
AluminiumThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Aluminium.Approved
Aluminium acetoacetateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Aluminium acetoacetate.Experimental
Aluminium glycinateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Aluminium glycinate.Experimental
Aluminum hydroxideThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Aluminum hydroxide.Approved
AsenapineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Asenapine.Approved
Bismuth SubcitrateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Bismuth Subcitrate.Approved
Bismuth subnitrateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Bismuth subnitrate.Experimental
Calcium CarbonateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Calcium Carbonate.Approved
Calcium silicateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Calcium silicate.Experimental
CimetidineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Cimetidine.Approved
DexlansoprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Dexlansoprazole.Approved
DexrabeprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Dexrabeprazole.Experimental
DoxepinThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Doxepin.Approved
EpinastineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Epinastine.Approved, Investigational
EsomeprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Esomeprazole.Approved, Investigational
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Cysteamine.Approved
FamotidineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Famotidine.Approved
HydrotalciteThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Hydrotalcite.Experimental, Investigational
LansoprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Lansoprazole.Approved, Investigational
MagaldrateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magaldrate.Approved, Withdrawn
Magnesium HydroxideThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magnesium Hydroxide.Approved
Magnesium oxideThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magnesium oxide.Approved
Magnesium peroxideThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magnesium peroxide.Experimental
Magnesium silicateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magnesium silicate.Approved, Experimental
Magnesium TrisilicateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Magnesium Trisilicate.Approved
MethanthelineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Methantheline.Approved, Investigational
MetiamideThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Metiamide.Experimental
NizatidineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Nizatidine.Approved
OlanzapineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Olanzapine.Approved, Investigational
OmeprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Omeprazole.Approved, Investigational, Vet Approved
PantoprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Pantoprazole.Approved
PromethazineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Promethazine.Approved
RabeprazoleThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Rabeprazole.Approved, Investigational
RanitidineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Ranitidine.Approved
Roxatidine acetateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Roxatidine acetate.Approved, Investigational
Sodium bicarbonateThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Sodium bicarbonate.Approved
TromethamineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Tromethamine.Approved
Food Interactions
  • Avoid administration of delayed release cysteamine less than 30 minutes before and within 2 hours after ingesting food due to decreased bioavailability of cysteamine.

References

Synthesis Reference

Tethuharu Okazaki, Takeo Komukai, Saburo Uchikuga, "Process for preparing cysteamine-S-substituted compounds and derivatives thereof." U.S. Patent US4371472, issued September, 1969.

US4371472
General References
  1. Lukashin BP, Grebeniuk AN: [Comparative study of the radiation-protective effectiveness of low doses of cysteamine, heparin, and naphtizine in experiments on mice]. Radiats Biol Radioecol. 2001 May-Jun;41(3):310-2. [PubMed:11458646]
  2. Dohil R, Fidler M, Gangoiti JA, Kaskel F, Schneider JA, Barshop BA: Twice-daily cysteamine bitartrate therapy for children with cystinosis. J Pediatr. 2010 Jan;156(1):71-75.e1-3. doi: 10.1016/j.jpeds.2009.07.016. Epub . [PubMed:19775699]
External Links
Human Metabolome Database
HMDB02991
KEGG Drug
D03634
KEGG Compound
C01678
PubChem Compound
6058
PubChem Substance
46507730
ChemSpider
5834
BindingDB
7968
ChEBI
17141
ChEMBL
CHEMBL602
Therapeutic Targets Database
DAP001297
PharmGKB
PA449171
HET
DHL
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cysteamine
ATC Codes
S01XA21 — MercaptamineA16AA04 — Mercaptamine
AHFS Codes
  • 92:92.00 — Other Miscellaneous Therapeutic Agents
PDB Entries
2y8d / 3q1l / 3som / 4cg4 / 4pa5 / 5apr / 5ej0
FDA label
Download (115 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCystinosis, Nephropathic1
1, 2CompletedNot AvailableCystic Fibrosis (CF)1
1, 2CompletedTreatmentCystinosis, Nephropathic1
1, 2CompletedTreatmentFatty Liver1
2CompletedTreatmentCystinosis, Nephropathic1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentInherited Mitochondrial Disease, Including Leigh Syndrome1
2RecruitingTreatmentCystic Fibrosis (CF)1
3Active Not RecruitingTreatmentCystinosis, Nephropathic1
3CompletedTreatmentCystinosis, Nephropathic1
4CompletedTreatmentInfantile Neronal Ceroid Lipofuscinosis1
4RecruitingTreatmentCystinosis, Nephropathic1
Not AvailableCompletedNot AvailableCystinosis, Nephropathic1
Not AvailableCompletedTreatmentCorneal Cystine Crystals / Nephropathic Cyctinosis1
Not AvailableCompletedTreatmentCystinosis, Nephropathic1
Not AvailableTerminatedTreatmentMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
  • Mylan pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral150 mg
CapsuleOral150 mg/1
CapsuleOral50 mg/1
CapsuleOral50 mg
SolutionOphthalmic6.5 mg/mL
Capsule, delayed releaseOral25 mg
Capsule, delayed releaseOral75 mg
Capsule, delayed release pelletsOral25 mg/1
Capsule, delayed release pelletsOral75 mg/1
Prices
Unit descriptionCostUnit
Cystagon 150 mg capsule1.28USD capsule
Cystagon 50 mg capsule0.44USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9192590No2007-01-262027-01-26Us
US9198882No2007-01-262027-01-26Us
US8026284No2007-09-222027-09-22Us
US9233077No2014-06-172034-06-17Us
US9173851No2014-06-172034-06-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)98 °CPhysProp
water solubilityFreely soluble in water.From The Merck Index.
logP0.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility23.5 mg/mLALOGPS
logP0.01ALOGPS
logP-0.42ChemAxon
logS-0.52ALOGPS
pKa (Strongest Acidic)9.42ChemAxon
pKa (Strongest Basic)10.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area26.02 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity22.39 m3·mol-1ChemAxon
Polarizability8.65 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9378
Blood Brain Barrier+0.7618
Caco-2 permeable+0.7461
P-glycoprotein substrateNon-substrate0.7
P-glycoprotein inhibitor INon-inhibitor0.9634
P-glycoprotein inhibitor IINon-inhibitor0.9637
Renal organic cation transporterNon-inhibitor0.751
CYP450 2C9 substrateNon-substrate0.9035
CYP450 2D6 substrateNon-substrate0.5713
CYP450 3A4 substrateNon-substrate0.8282
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9396
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8091
Ames testNon AMES toxic0.8488
CarcinogenicityNon-carcinogens0.5197
BiodegradationNot ready biodegradable0.7564
Rat acute toxicity2.2165 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8358
hERG inhibition (predictor II)Non-inhibitor0.8686
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.29 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)GC-MSsplash10-00di-1900000000-287334efed4c27d47e62
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)GC-MSsplash10-00di-1900000000-e26f666cab18d523e475
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)GC-MSsplash10-00di-7900000000-25e27a3413a3e9bd6e86
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-00dr-3900000000-5f3c0dc6b99382c852e2
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-1900000000-287334efed4c27d47e62
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-1900000000-e26f666cab18d523e475
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-7900000000-25e27a3413a3e9bd6e86
GC-MS Spectrum - GC-MSGC-MSsplash10-00dr-3900000000-5f3c0dc6b99382c852e2
GC-MS Spectrum - GC-MSGC-MSsplash10-00dr-3900000000-5f3c0dc6b99382c852e2
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-2900000000-ba8ae281d3d77ff202c1
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-03di-9000000000-0fdf5bdcf8a4a1bf9afb
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-03di-9000000000-f99f2f10c6728595d6ea
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)LC-MS/MSsplash10-01t9-9000000000-fa7f96e00debe1bebf70
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkylthiols. These are organic compounds containing the thiol functional group linked to an alkyl chain.
Kingdom
Organic compounds
Super Class
Organosulfur compounds
Class
Thiols
Sub Class
Alkylthiols
Direct Parent
Alkylthiols
Alternative Parents
Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
Alkylthiol / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Primary amine / Organonitrogen compound / Primary aliphatic amine / Amine / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
thiol, amine (CHEBI:17141) / Biogenic amines (C01678) / a thiol (CPD-239)

Targets

1. Cystine
Kind
Amino acid
Organism
Human
Pharmacological action
Unknown
Actions
Cleavage
References
  1. Omran Z, Kay G, Di Salvo A, Knott RM, Cairns D: PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis. Bioorg Med Chem Lett. 2011 Jan 1;21(1):45-7. doi: 10.1016/j.bmcl.2010.11.085. Epub 2010 Nov 21. [PubMed:21147534]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Hormone activity
Specific Function
Somatostatin inhibits the release of somatotropin.
Gene Name
SST
Uniprot ID
P61278
Uniprot Name
Somatostatin
Molecular Weight
12735.395 Da
References
  1. Ahren B, Bottcher G, Ekman R, Sundler F: Cysteamine and the endocrine pancreas: immunocytochemical, immunochemical, and functional aspects. Cell Tissue Res. 1989 Apr;256(1):159-66. [PubMed:2653642]
  2. McIntosh CH, Bakich V, Bokenfohr K, DiScala-Guenot D, Kwok YN, Brown JC: Cysteamine-induced reduction in gastrointestinal somatostatin: evidence for a region-specific loss in immunoreactivity. Regul Pept. 1988 Jun;21(3-4):205-18. [PubMed:2901134]
  3. Terry LC, Craig R: Cysteamine effects on monoamines, dopamine-beta-hydroxylase and the hypothalamic-pituitary axis. Neuroendocrinology. 1985 Dec;41(6):467-75. [PubMed:4080089]
  4. McIntosh C, Bakich V, Trotter T, Kwok YN, Nishimura E, Pederson R, Brown J: Effect of cysteamine on secretion of gastrin and somatostatin from the rat stomach. Gastroenterology. 1984 May;86(5 Pt 1):834-8. [PubMed:6142843]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Receptor activity
Specific Function
Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu-31, Pro-34] N...
Gene Name
NPY2R
Uniprot ID
P49146
Uniprot Name
Neuropeptide Y receptor type 2
Molecular Weight
42730.69 Da
References
  1. Li W, Hexum TD: Cysteamine selectively enhances neuropeptide Y2 receptor binding activity. Biochem Biophys Res Commun. 1992 Apr 15;184(1):380-6. [PubMed:1314592]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Peroxidase activity
Specific Function
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name
MPO
Uniprot ID
P05164
Uniprot Name
Myeloperoxidase
Molecular Weight
83867.71 Da
References
  1. Svensson BE: Abilities of peroxidases to catalyse peroxidase-oxidase oxidation of thiols. Biochem J. 1988 Dec 15;256(3):757-62. [PubMed:2852004]
  2. Svensson BE, Graslund A, Strom G, Moldeus P: Thiols as peroxidase substrates. Free Radic Biol Med. 1993 Feb;14(2):167-75. [PubMed:8381104]
  3. Svensson BE, Lindvall S: Myeloperoxidase-oxidase oxidation of cysteamine. Biochem J. 1988 Jan 15;249(2):521-30. [PubMed:2829860]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34