Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C6H18N4 |
| Molecular Weight | 146.2339 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NCCNCCNCCN
InChI
InChIKey=VILCJCGEZXAXTO-UHFFFAOYSA-N
InChI=1S/C6H18N4/c7-1-3-9-5-6-10-4-2-8/h9-10H,1-8H2
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2363057 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27613237 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | SYPRINE Approved UseSYPRINE 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 Date1985 |
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| Preventing | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.39 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
1.55 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
5.61 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.08 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
11.14 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
31.03 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.06 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
10.37 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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 |
|
14.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19602718 |
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
| Dose | Population | Adverse 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) Health Status: unhealthy Age Group: 10.5 (range 6.6–15.6) Sex: M+F Sources: |
Disc. AE: Allergic rash... AEs leading to discontinuation/dose reduction: Allergic rash (3 patients) Sources: |
1000 mg 2 times / day multiple, oral Recommended Dose: 1000 mg, 2 times / day Route: oral Route: multiple Dose: 1000 mg, 2 times / day Sources: |
unhealthy, 13 to 33 Health Status: unhealthy Age Group: 13 to 33 Sex: M+F 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) Health Status: healthy Age Group: 28.6 ± 11.1 (18-44) Sex: M+F Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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) Health Status: unhealthy Age Group: 10.5 (range 6.6–15.6) Sex: M+F Sources: |
| Thrombocytopenia | mild, 1 patient Disc. AE |
1000 mg 2 times / day multiple, oral Recommended Dose: 1000 mg, 2 times / day Route: oral Route: multiple Dose: 1000 mg, 2 times / day Sources: |
unhealthy, 13 to 33 Health Status: unhealthy Age Group: 13 to 33 Sex: M+F Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| A case study: identifying a new case of Wilson's disease. | 2005-12 |
|
| An improvement in the bending ability of a hinged trisaccharide with the assistance of a sugar-sugar interaction. | 2005-11-04 |
|
| The passivation of pyrrhotite by surface coating. | 2005-11 |
|
| Pharmacological studies on mechanisms of aminophylline-induced seizures in rats. | 2005-10 |
|
| Combination treatment with penicillamine and trientine in a patient with Wilson's disease. | 2005-10 |
|
| Two male patients with Wilson's disease treated using trientine and iron reduction therapy. | 2005-10 |
|
| [Acute liver failure and hemolysis in a 16-year-old woman. First manifestation of Wilson's disease]. | 2005-09-15 |
|
| Anticopper therapy against cancer and diseases of inflammation and fibrosis. | 2005-08-15 |
|
| 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. | 2005-08-08 |
|
| Combination of copper-chelating agent, trientine, and methotrexate attenuates colorectal carcinoma development and angiogenesis in mice. | 2005-07 |
|
| A copper chelating agent suppresses carbonyl stress in diabetic rat lenses. | 2005-06-15 |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005-06 |
|
| [DNA repair and antioxidant defence in the repair-deficient human cells (Marfan's syndrome) after gamma-irradiation]. | 2005-05-24 |
|
| 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. | 2005-05 |
|
| Wilson's disease with depression and parkinsonism. | 2005-04 |
|
| Improvement of cardiovascular autonomic dysfunction following anti-copper therapy in Wilson's disease. | 2005-04 |
|
| Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery. | 2005-03-09 |
|
| Wilson disease in septuagenarian siblings: Raising the bar for diagnosis. | 2005-03 |
|
| Wilson's disease: clinical, genetic and pharmacological findings. | 2005-02-09 |
|
| Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease. | 2005-01-01 |
|
| Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment. | 2005 |
|
| Pathophysiology and clinical features of Wilson disease. | 2004-12 |
|
| Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in hepatic cells of Long-Evans Cinnamon rats. | 2004-11-01 |
|
| [Wilson's disease and its pharmacological treatment]. | 2004-11 |
|
| Regeneration of the heart in diabetes by selective copper chelation. | 2004-09 |
|
| Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease. | 2004-08-24 |
|
| 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. | 2004-07-30 |
|
| New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. | 2004-06-23 |
|
| Metal contents of liver parenchyma after percutaneous ethanol injection or radiofrequency ablation in patients with hepatocellular carcinoma before and after trientine hydrochloride therapy. | 2004-06 |
|
| Cleavage of the peptide bond of beta-alanyl-L-histidine (carnosine) induced by a Co(III)-amine complexes: reaction, structure and mechanism. | 2004-05-07 |
|
| [Wilson's disease with severe neurological manifestations: response to trientine plus zinc therapy]. | 2004-05 |
|
| Synthesis and characterisation of cyclopentadienyl complexes of barium: precursors for atomic layer deposition of BaTiO3. | 2004-04-21 |
|
| The effects of network structure on the resistance of silane coupling agent layers to water-assisted crack growth. | 2004-04-13 |
|
| 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. | 2004-02-20 |
|
| Review article: diagnosis and current therapy of Wilson's disease. | 2004-01-15 |
|
| [Wilson disease]. | 2004-01 |
|
| 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 |
|
| [Wilson disease in 2003]. | 2003-12-14 |
|
| [Differentiation of activity of a superoxide dismutase inhibitor in human cells exposed to radiation, chemical mutagens and radioadaptive response]. | 2003-12 |
|
| Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zinc. | 2003-12 |
|
| Current and future therapy in haemochromatosis and Wilson's disease. | 2003-12 |
|
| Triethylene tetraamine: a novel telomerase inhibitor. | 2003-11-17 |
|
| Ferromagnetism in a dinuclear nickel(II) complex containing triethylenetetramine and tricyanomethanide. | 2003-11-03 |
|
| [Electrophysiological impairment profile of patients with Wilson's disease]. | 2003-10 |
|
| Bis(dicyanamido)(diethylenetriamine-kappa(3)N)copper(II) and (dicyanamido)(triethylenetetramine-kappa(4)N)copper(II) dicyanamide. | 2003-10 |
|
| Influence of electrolyte composition on the electroosmotic flow and electrophoretic mobility of proteins and peptides. | 2003-09-26 |
|
| Treatment of Wilson's disease. | 2003-08 |
|
| [Pathogenesis and treatment of Wilson's disease]. | 2003 |
|
| [Wilson's disease]. | 2003 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19959910
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.
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| Classification Tree | Code System | Code | ||
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CFR |
21 CFR 176.170
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NDF-RT |
N0000175472
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NCI_THESAURUS |
C62357
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WHO-ATC |
A16AX12
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NDF-RT |
N0000175473
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LIVERTOX |
NBK548119
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C66633
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39501
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DB06824
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100000077721
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1002
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D014266
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4664
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10798
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TRIETHYLENETETRAMINE
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SJ76Y07H5F
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5565
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SUB04953MIG
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Trientine
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DTXSID9023702
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SUB11281MIG
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2738
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m11098
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CHEMBL609
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SJ76Y07H5F
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
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