Triethylenetetramine pharmacology and its clinical applications.

Article Details

Citation

Lu J

Triethylenetetramine pharmacology and its clinical applications.

Mol Cancer Ther. 2010 Sep;9(9):2458-67. doi: 10.1158/1535-7163.MCT-10-0523. Epub 2010 Jul 26.

PubMed ID
20660601 [ View in PubMed
]
Abstract

Triethylenetetramine (TETA), a Cu(II)-selective chelator, is commonly used for the treatment of Wilson's disease. Recently, it has been shown that TETA can be used in the treatment of cancer because it possesses telomerase inhibiting and anti-angiogenesis properties. Although TETA has been used in the treatment of Wilson's disease for decades, a comprehensive review on TETA pharmacology does not exist. TETA is poorly absorbed with a bioavailability of 8 to 30%. It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. It is mainly excreted in urine as the unchanged parent drug and two acetylated metabolites. It has a relatively short half-life (2 to 4 hours) in humans. The most recent discoveries in TETA pharmacology show that the major pharmacokinetic parameters are not associated with the acetylation phenotype of N-acetyltransferase 2, the traditionally regarded drug acetylation enzyme, and the TETA-metabolizing enzyme is actually spermidine/spermine acetyltransferase. This review also covers the current preclinical and clinical application of TETA. A much needed overview and up-to-date information on TETA pharmacology is provided for clinicians or cancer researchers who intend to embark on cancer clinical trials using TETA or its close structural analogs.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
TriethylenetetramineDiamine acetyltransferase 1ProteinHumans
Unknown
Substrate
Details
Drug Interactions
DrugsInteraction
Triethylenetetramine
Ethoxzolamide
The excretion of Triethylenetetramine can be increased when combined with Ethoxzolamide.
Triethylenetetramine
Methazolamide
The excretion of Triethylenetetramine can be increased when combined with Methazolamide.
Triethylenetetramine
Acetazolamide
The excretion of Triethylenetetramine can be increased when combined with Acetazolamide.
Triethylenetetramine
Zonisamide
The excretion of Triethylenetetramine can be increased when combined with Zonisamide.
Triethylenetetramine
Diclofenamide
The excretion of Triethylenetetramine can be increased when combined with Diclofenamide.