U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C6H18N4
Molecular Weight 146.2342
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIENTINE

SMILES

C(CNCCNCCN)N

InChI

InChIKey=VILCJCGEZXAXTO-UHFFFAOYSA-N
InChI=1S/C6H18N4/c7-1-3-9-5-6-10-4-2-8/h9-10H,1-8H2

HIDE SMILES / InChI
Trientine, also known as triethylenetatramine or abbreviation TETA, is a highly selective divalent Cu(II) chelator and orphan drug that reverses copper overload in tissues. It was approved as second-line pharmacotherapy for Wilson's disease. Wilson's disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper but when their capacity is exceeded copper is released into the blood and is taken up into extrahepatic sites. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy. In addition, TETA is in a clinical trial phase II for the prevention of the Macular Edema after Cataract Surgery. TETA is also considered a potential chemotherapeutic agent as it could be a telomerase inhibitor. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.

CNS Activity

Curator's Comment:: . Trientine has been found to lower serum iron and does cross the blood brain barrier, but results in a few cases have been mixed

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2363057
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SYPRINE

Approved Use

SYPRINE is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with SYPRINE is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defined. SYPRINE and penicillamine cannot be considered interchangeable. SYPRINE should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects. Unlike penicillamine, SYPRINE is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, SYPRINE was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment. SYPRINE is not indicated for treatment of biliary cirrhosis.

Launch Date

5.00256014E11
Preventing
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.55 mg/L
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.39 mg/L
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.69 mg/L
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.61 mg/L
1800 mg 2 times / day steady-state, oral
dose: 1800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
11.14 mg × h/L
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.08 mg × h/L
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.77 mg × h/L
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
31.03 mg × h/L
1800 mg 2 times / day steady-state, oral
dose: 1800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.37 h
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.06 h
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.35 h
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.21 h
1800 mg 2 times / day steady-state, oral
dose: 1800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TRIENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources:
unhealthy, 10.5 (range 6.6–15.6)
n = 16
Health Status: unhealthy
Condition: Wilson disease
Age Group: 10.5 (range 6.6–15.6)
Sex: M+F
Population Size: 16
Sources:
Disc. AE: Allergic rash...
AEs leading to
discontinuation/dose reduction:
Allergic rash (3 patients)
Sources:
1000 mg 2 times / day multiple, oral (max)
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy, 13 to 33
n = 7
Health Status: unhealthy
Condition: Wilson disease
Age Group: 13 to 33
Sex: M+F
Population Size: 7
Sources:
Disc. AE: Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (mild, 1 patient)
Sources:
1800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1800 mg, 2 times / day
Sources:
healthy, 28.6 ± 11.1 (18-44)
n = 8
Health Status: healthy
Age Group: 28.6 ± 11.1 (18-44)
Sex: M+F
Population Size: 8
Sources:
AEs

AEs

AESignificanceDosePopulation
Allergic rash 3 patients
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources:
unhealthy, 10.5 (range 6.6–15.6)
n = 16
Health Status: unhealthy
Condition: Wilson disease
Age Group: 10.5 (range 6.6–15.6)
Sex: M+F
Population Size: 16
Sources:
Thrombocytopenia mild, 1 patient
Disc. AE
1000 mg 2 times / day multiple, oral (max)
Recommended
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy, 13 to 33
n = 7
Health Status: unhealthy
Condition: Wilson disease
Age Group: 13 to 33
Sex: M+F
Population Size: 7
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Pathogenesis and treatment of Wilson's disease].
2003
[Wilson's disease].
2003
[Contact allergy to epoxy resins plastics based on materials collected by the Nofer Institute of Occupational Medicine].
2003
Treatment of Wilson's disease.
2003 Aug
Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells.
2003 Aug
Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zinc.
2003 Dec
Current and future therapy in haemochromatosis and Wilson's disease.
2003 Dec
[Peripheral haemosiderosis of the central nervous system].
2003 Jul
Triethylene tetraamine: a novel telomerase inhibitor.
2003 Nov 17
Ferromagnetism in a dinuclear nickel(II) complex containing triethylenetetramine and tricyanomethanide.
2003 Nov 3
[Electrophysiological impairment profile of patients with Wilson's disease].
2003 Oct
Bis(dicyanamido)(diethylenetriamine-kappa(3)N)copper(II) and (dicyanamido)(triethylenetetramine-kappa(4)N)copper(II) dicyanamide.
2003 Oct
Surface grafting of glycidyl methacrylate on silica gel and polyethylene beads.
2003 Sep
Wilson disease.
2003 Sep
Synthesis and characterization of a novel organically templated open framework zirconogermanate with three- and seven-membered rings.
2003 Sep 22
Influence of electrolyte composition on the electroosmotic flow and electrophoretic mobility of proteins and peptides.
2003 Sep 26
The copper-chelating agent, trientine, attenuates liver enzyme-altered preneoplastic lesions in rats by angiogenesis suppression.
2003 Sep-Oct
A new bifunctional chelating agent conjugated with monoclonal antibody and labelled with technetium-99m for targeted scintigraphy: 6-(4-isothiocyanatobenzyl)-5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane.
2004
Effects of triethylene tetraamine on telomerase activity and proliferation in HeLa cells.
2004
The effects of network structure on the resistance of silane coupling agent layers to water-assisted crack growth.
2004 Apr 13
Synthesis and characterisation of cyclopentadienyl complexes of barium: precursors for atomic layer deposition of BaTiO3.
2004 Apr 21
Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease.
2004 Aug 24
Pathophysiology and clinical features of Wilson disease.
2004 Dec
Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators.
2004 Jan
Review article: diagnosis and current therapy of Wilson's disease.
2004 Jan 15
Affinity chromatography with monolithic capillary columns I. Polymethacrylate monoliths with immobilized mannan for the separation of mannose-binding proteins by capillary electrochromatography and nano-scale liquid chromatography.
2004 Jul 30
Metal contents of liver parenchyma after percutaneous ethanol injection or radiofrequency ablation in patients with hepatocellular carcinoma before and after trientine hydrochloride therapy.
2004 Jun
New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.
2004 Jun 23
[Wilson's disease with severe neurological manifestations: response to trientine plus zinc therapy].
2004 May
Cleavage of the peptide bond of beta-alanyl-L-histidine (carnosine) induced by a Co(III)-amine complexes: reaction, structure and mechanism.
2004 May 7
[Wilson's disease and its pharmacological treatment].
2004 Nov
Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in hepatic cells of Long-Evans Cinnamon rats.
2004 Nov 1
Regeneration of the heart in diabetes by selective copper chelation.
2004 Sep
Improvement of cardiovascular autonomic dysfunction following anti-copper therapy in Wilson's disease.
2005 Apr
Anticopper therapy against cancer and diseases of inflammation and fibrosis.
2005 Aug 15
Template-assisted solvothermal synthesis of five copper(I)-thioantimonate(III) composites: crystal structures and optical and thermal properties of (C6N2H18)0.5Cu2SbS3, (C4N3H15)0.5Cu2SbS3, (C8N4H22)0.5Cu2SbS3, (C4N3H14)Cu3Sb2S5, and (C6)N4H20)0.5Cu3Sb2S5.
2005 Aug 8
A case study: identifying a new case of Wilson's disease.
2005 Dec
Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease.
2005 Jan 1
Combination of copper-chelating agent, trientine, and methotrexate attenuates colorectal carcinoma development and angiogenesis in mice.
2005 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Wilson disease in septuagenarian siblings: Raising the bar for diagnosis.
2005 Mar
[DNA repair and antioxidant defence in the repair-deficient human cells (Marfan's syndrome) after gamma-irradiation].
2005 Mar-Apr
Demonstration of a hyperglycemia-driven pathogenic abnormality of copper homeostasis in diabetes and its reversibility by selective chelation: quantitative comparisons between the biology of copper and eight other nutritionally essential elements in normal and diabetic individuals.
2005 May
The passivation of pyrrhotite by surface coating.
2005 Nov
An improvement in the bending ability of a hinged trisaccharide with the assistance of a sugar-sugar interaction.
2005 Nov 4
A copper chelating agent suppresses carbonyl stress in diabetic rat lenses.
2005 Nov-Dec
Pharmacological studies on mechanisms of aminophylline-induced seizures in rats.
2005 Oct
Combination treatment with penicillamine and trientine in a patient with Wilson's disease.
2005 Oct
Two male patients with Wilson's disease treated using trientine and iron reduction therapy.
2005 Oct
[Acute liver failure and hemolysis in a 16-year-old woman. First manifestation of Wilson's disease].
2005 Sep 15
Patents

Sample Use Guides

The recommended initial dose is 500-750 mg/day for pediatric patients and 750-1250 mg/day for adults given in divided doses two, three or four times daily. This may be increased to a maximum of 2000 mg/day for adults or 1500 mg/day for pediatric patients age 12 or under. The daily dose of Syprine should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dL. Optimal long-term maintenance dosage should be determined at 6-12 month intervals
Route of Administration: Oral
It was reported, that treatment with trientine inhibited tumor growth in a murine transplantation model using fibrosarcoma and induces apoptosis in tumor cells in vivo and in vitro. When fibrosarcoma cells were treated with 10 mM trientine, the activities of p38 MAPK in treated cells were approximately 3-4 times higher than those in untreated cells. Proportions of cells in which apoptosis was induced by trientine increased in an incubation time-dependent manner from days 2 to 6.
Name Type Language
TRIENTINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NSC-443
Code English
TRIENTINE [INN]
Common Name English
TRIENTINE [WHO-DD]
Common Name English
1,2-ETHANEDIAMINE, N,N'-BIS(2-AMINOETHYL)-
Systematic Name English
TRIENTINE [MI]
Common Name English
TRETHYLENETETRAMINE
Common Name English
TRIETHYLENETETRAMINE
HSDB  
Systematic Name English
TRIETHYLENE TETRAMINE
Common Name English
TRIETHYLENE TETRAAMINE
Common Name English
TRIENTINE [VANDF]
Common Name English
TRIETHYLENETETRAMINE [HSDB]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 176.170
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
NDF-RT N0000175472
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
NCI_THESAURUS C62357
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
WHO-ATC A16AX12
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
NDF-RT N0000175473
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
LIVERTOX 997
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C66633
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
DRUG BANK
DB06824
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
HSDB
1002
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
MESH
D014266
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
CAS
112-24-3
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
ECHA (EC/EINECS)
203-950-6
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
INN
4664
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
RXCUI
10798
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
TRIETHYLENETETRAMINE
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
PUBCHEM
5565
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
EVMPD
SUB04953MIG
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
LACTMED
Trientine
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
EPA CompTox
112-24-3
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY
EVMPD
SUB11281MIG
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
DRUG CENTRAL
2738
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
MERCK INDEX
M11098
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL609
Created by admin on Sat Jun 26 01:40:42 UTC 2021 , Edited by admin on Sat Jun 26 01:40:42 UTC 2021
PRIMARY
FDA UNII
SJ76Y07H5F
Created by admin on Sat Jun 26 01:40:43 UTC 2021 , Edited by admin on Sat Jun 26 01:40:43 UTC 2021
PRIMARY