Repositioning Candidate Details
| Candidate ID: | R1107 |
| Source ID: | DB06824 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Triethylenetetramine |
| Synonyms: | TETA; Trien; Trientine |
| Molecular Formula: | C6H18N4 |
| SMILES: | NCCNCCNCCN |
| Structure: |
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| DrugBank Description: | Triethylenetatramine (TETA) is a highly selective divalent Cu(II) chelator and orphan drug that revereses copper overload in tissues. Its salt form, trientine (triethylenetetramine dihydrochloride or 2,2,2-tetramine) was introduced in 1969 as an alternative to D-penicillamine. It consists of a polyamine-like structure different from D-penicillamine, as it lack sulfhydryl groups. It was previously approved by FDA in 1985 as second-line pharmacotherapy for Wilson's disease. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy, even with patients with decompensated liver disease at the outset, and prolonged TETA treatment is not associated with adverse effects as expected in penicillamine treatment. Its clinical applications on cancer, diabetes mellitus, Alzheimer's disease and vascular demetia are being studied. |
| CAS Number: | 112-24-3 |
| Molecular Weight: | 146.2339 |
| DrugBank Indication: | Trientine is a copper chelator used in the treatment of Wilson's disease as an alternative to D-penicillamine. It tends to be used in patients who are experiencing serious adverse effects from penicillamine therapy or intolerance of penicillamine. |
| DrugBank Pharmacology: | TETA is a selective copper (II) chelator. tightly binds and facilitates systemic elimination of Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency even after prolonged use. It may also act as an antioxidant as it suppresses the copper-mediated oxidative stress. TETA not only increases urinary Cu excretion, but also decreases intestinal copper absorption by 80%. |
| DrugBank MoA: | Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar ring as copper displays enhanced ligand binding properties for nitrogen compared to oxygen. It binds Cu(II) very tightly, having a dissociation constant from Cu(II) of 10^−15 mol/L at pH 7.0 . TETA reacts in a stoichiometric ratio 1:1 with copper and is also able to complex with iron and zinc in vivo. TETA is considered a potential chemotherapeutic agent as it could be a telomerase inhibitor because it is a ligand for G-quadruplex, and stabilizes both intra- and intermolecular G-quadruplexes. It may mediate a selective inhibitory effect or cytotoxicity on tumor growth. 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. |
| Targets: | -- |
| Inclusion Criteria: | Therapeutic strategy associated |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |