Details
Stereochemistry | ACHIRAL |
Molecular Formula | C6H18N4.4ClH |
Molecular Weight | 292.0777 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C(CNCCNCCN)N.Cl.Cl.Cl.Cl
InChI
InChIKey=OKHMDSCYUWAQPT-UHFFFAOYSA-N
InChI=1S/C6H18N4.4ClH/c7-1-3-9-5-6-10-4-2-8;;;;/h9-10H,1-8H2;4*1H
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 |
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 |
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 Date5.00256014E11 |
|||
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 |
---|---|---|
Personality traits in treated Wilson's disease determined by means of the Karolinska Scales of Personality (KSP). | 2001 Sep |
|
[The role of copper in tumor angiogenesis--clinical implications]. | 2002 |
|
Diagnosis and treatment of Wilson's disease. | 2002 Feb |
|
Roles of metallothionein in copper homeostasis: responses to Cu-deficient diets in mice. | 2002 Jan 15 |
|
The crystal structure of N(1)-[2-(2-amino-ethylamino)-ethyl]-ethane-1,2-diamine (polyamines) binding to the minor groove of d(CGCGCG)(2), hexamer at room temperature. | 2002 Jul 17 |
|
Liver targeting of plasmid DNA by pullulan conjugation based on metal coordination. | 2002 Oct 4 |
|
[The transport mechanism of polycationic compounds across intestinal and renal cell membrane]. | 2002 Sep |
|
[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 |
|
[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 |
|
[Wilson's disease: physiopathological, clinical and therapeutic considerations]. | 2003 Jan |
|
Synthesis of uniform anatase TiO2 nanoparticles by gel-sol method. 4. Shape control. | 2003 Mar 1 |
|
Regulation of copper absorption by copper availability in the Caco-2 cell intestinal model. | 2003 May |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Regeneration of the heart in diabetes by selective copper chelation. | 2004 Sep |
|
Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment. | 2005 |
|
Wilson's disease with depression and parkinsonism. | 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 |
|
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 |
|
[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
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Jun 26 06:37:37 UTC 2021
by
admin
on
Sat Jun 26 06:37:37 UTC 2021
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Record UNII |
7360URE56Q
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Record Status |
Validated (UNII)
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Record Version |
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Common Name | English |
Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
492915
Created by
admin on Sat Jun 26 06:37:38 UTC 2021 , Edited by admin on Sat Jun 26 06:37:38 UTC 2021
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EU-Orphan Drug |
EU/3/15/1471
Created by
admin on Sat Jun 26 06:37:38 UTC 2021 , Edited by admin on Sat Jun 26 06:37:38 UTC 2021
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Code System | Code | Type | Description | ||
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225-604-3
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4961-40-4
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7360URE56Q
Created by
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71434
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4961-40-4
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SUB77343
Created by
admin on Sat Jun 26 06:37:38 UTC 2021 , Edited by admin on Sat Jun 26 06:37:38 UTC 2021
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