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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
Structure of TRIENTINE

SMILES

NCCNCCNCCN

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

Molecular Formula C6H18N4
Molecular Weight 146.2339
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SYPRINE
Preventing
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
1.55 mg/L
600 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
0.39 mg/L
100 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
0.69 mg/L
300 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
5.61 mg/L
1800 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
11.14 mg × h/L
600 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
2.08 mg × h/L
100 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
3.77 mg × h/L
300 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
31.03 mg × h/L
1800 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
10.37 h
600 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
5.06 h
100 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
5.35 h
300 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens
14.21 h
1800 mg 2 times / day steady-state, oral
TRIENTINE plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
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
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
Record UNII
SJ76Y07H5F
Record Status Validated (UNII)
Record Version