Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C6H18N4.C2H4O2 |
| Molecular Weight | 206.2859 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)=O.NCCNCCNCCN
InChI
InChIKey=LZQWCUSWOKKCIN-UHFFFAOYSA-N
InChI=1S/C6H18N4.C2H4O2/c7-1-3-9-5-6-10-4-2-8;1-2(3)4/h9-10H,1-8H2;1H3,(H,3,4)
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 |
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 |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|---|---|---|---|---|
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 |
|
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 |
|
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) 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
| 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) 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: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| [The role of copper in tumor angiogenesis--clinical implications]. | 2002 |
|
| [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 |
|
| [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 |
|
| The effect of triethylenetetraamine (Trien) on the ion flotation of Cu(2+) and Ni(2+). | 2003 Feb 15 |
|
| [Peripheral haemosiderosis of the central nervous system]. | 2003 Jul |
|
| Antiangiogenic therapy through copper chelation. | 2003 Jun |
|
| Synthesis of uniform anatase TiO2 nanoparticles by gel-sol method. 4. Shape control. | 2003 Mar 1 |
|
| Ferromagnetism in a dinuclear nickel(II) complex containing triethylenetetramine and tricyanomethanide. | 2003 Nov 3 |
|
| Wilson disease. | 2003 Sep |
|
| Synthesis and characterization of a novel organically templated open framework zirconogermanate with three- and seven-membered rings. | 2003 Sep 22 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment. | 2005 |
|
| Wilson's disease with depression and parkinsonism. | 2005 Apr |
|
| 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 |
|
| Wilson's disease: clinical, genetic and pharmacological findings. | 2005 Jan-Mar |
|
| 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 |
|
| Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery. | 2005 Mar 9 |
|
| [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.
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48P82SYS6Z
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31681-10-4
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19710895
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22379-16-4
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ACTIVE MOIETY
SUBSTANCE RECORD
