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Details

Stereochemistry ACHIRAL
Molecular Formula C6H18N4.2ClH
Molecular Weight 219.1559
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIENTINE HYDROCHLORIDE

SMILES

C(CNCCNCCN)N.Cl.Cl

InChI

InChIKey=WYHIICXRPHEJKI-UHFFFAOYSA-N
InChI=1S/C6H18N4.2ClH/c7-1-3-9-5-6-10-4-2-8;;/h9-10H,1-8H2;2*1H

HIDE SMILES / InChI

Molecular Formula C6H18N4
Molecular Weight 146.2342
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
[The role of copper in tumor angiogenesis--clinical implications].
2002
[Wilson's disease].
2003
[Contact allergy to epoxy resins plastics based on materials collected by the Nofer Institute of Occupational Medicine].
2003
Interactions of diethylenetriaminepentaacetic acid (dtpa) and triethylenetetraaminehexaacetic acid (ttha) with major components of natural waters.
2003 Apr
Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells.
2003 Aug
[Differentiation of activity of a superoxide dismutase inhibitor in human cells exposed to radiation, chemical mutagens and radioadaptive response].
2003 Dec
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
[Wilson disease in 2003].
2003 Dec 14
The efficacy of trientine or ascorbate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice.
2003 Feb
Separation of proteins on polymeric stationary phases grafted with various amine groups.
2003 Feb 14
The effect of triethylenetetraamine (Trien) on the ion flotation of Cu(2+) and Ni(2+).
2003 Feb 15
Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation.
2003 Jan-Mar
[Peripheral haemosiderosis of the central nervous system].
2003 Jul
Antiangiogenic therapy through copper chelation.
2003 Jun
Wilson's disease: the importance of measuring serum caeruloplasmin non-immunologically.
2003 Mar
Synthesis of uniform anatase TiO2 nanoparticles by gel-sol method. 4. Shape control.
2003 Mar 1
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
The effects of network structure on the resistance of silane coupling agent layers to water-assisted crack growth.
2004 Apr 13
Pathophysiology and clinical features of Wilson disease.
2004 Dec
Accelerated Koenigs-Knorr glucuronidation of a deactivated nitrophenol: unveiling the role of polyamine additive 1,1,4,7,10,10-hexamethyltriethylenetetramine through design of experiments.
2004 Feb 20
[Wilson disease].
2004 Jan
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
New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.
2004 Jun 23
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
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Wilson disease in septuagenarian siblings: Raising the bar for diagnosis.
2005 Mar
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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:02:15 UTC 2021
Edited
by admin
on Fri Jun 25 21:02:15 UTC 2021
Record UNII
HC3NX54582
Record Status Validated (UNII)
Record Version
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Name Type Language
TRIENTINE HYDROCHLORIDE
JAN   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
USAN  
Official Name English
TRIENTINE DIHYDROCHLORIDE
MART.   MI   WHO-DD  
Common Name English
TRIENTINE HYDROCHLORIDE [USAN]
Common Name English
TRIENTINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
TRIENTINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
TRIENTINE DIHYDROCHLORIDE [WHO-DD]
Common Name English
TRIENTINE HYDROCHLORIDE [USP-RS]
Common Name English
TRIENTINE DIHYDROCHLORIDE [MART.]
Common Name English
MK-0681
Code English
TRIETHYLENETETRAMINE DIHYDROCHLORIDE
Systematic Name English
SYPRINE
Brand Name English
1,2-ETHANEDIAMINE, N,N'-BIS(2-AMINOETHYL)-, DIHYDROCHLORIDE
Common Name English
TRIENTINE HCL
Common Name English
TRIENTINE DIHYDROCHLORIDE [MI]
Common Name English
TRIENTINE HYDROCHLORIDE [VANDF]
Common Name English
TRIENTINE HYDROCHLORIDE [JAN]
Common Name English
TRIETHYLENE TETRAMINE DIHYDROCHLORIDE
Common Name English
NSC-759164
Code English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
NCI_THESAURUS C62357
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
FDA ORPHAN DRUG 4884
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
EU-Orphan Drug EU/3/03/172
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
FDA ORPHAN DRUG 301210
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
Code System Code Type Description
EVMPD
SUB04953MIG
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
USP_CATALOG
1683504
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY USP-RS
FDA UNII
HC3NX54582
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
MERCK INDEX
M11098
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL609
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
ECHA (EC/EINECS)
253-854-3
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
RXCUI
235370
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY RxNorm
CAS
38260-01-4
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
EPA CompTox
38260-01-4
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
PUBCHEM
71433
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
NCI_THESAURUS
C61987
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
DRUG BANK
DBSALT001269
Created by admin on Fri Jun 25 21:02:15 UTC 2021 , Edited by admin on Fri Jun 25 21:02:15 UTC 2021
PRIMARY
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