Research Article Details
| Article ID: | A23266 |
| PMID: | 23915136 |
| Source: | Thyroid |
| Title: | Thyroid hormone analogues: where do we stand in 2013? |
| Abstract: | Thyroid hormones (THs) are important in the development and maintenance of lipid and energy homeostasis. THs act through two closely related TH receptors (TRs α and β), which are conditional transcription factors. Recently, TH analogues or thyromimetics with varying degrees of TR subtype and liver uptake selectivity have been developed. These compounds exert beneficial effects of TH excess states without many undesirable TR-dependent side effects. Several selective TR modulators (STRMs) showed exceptionally promising results in lowering serum cholesterol in preclinical animal models and human clinical studies. Moreover, some first generation STRMs elicit other potentially beneficial effects on obesity, glucose metabolism, and nonalcoholic fatty liver disease (NAFLD). While it was initially thought that STRMs would be an effective long-term therapy to combat elevated cholesterol, possibly in conjunction with another cholesterol-lowering therapy, the statins, three major first generation STRMs failed to progress beyond early phase III human trials. The aim of this review is to discuss how STRMs work, their actions in preclinical animal models and human clinical trials, why they did not progress beyond clinical trials as cholesterol-lowering therapeutics, whether selective TR modulation continues to hold promise for dyslipidemias, and whether members of this drug class could be applied to the treatment of other aspects of metabolic syndrome and human genetic disease. |
| DOI: | 10.1089/thy.2012.0458 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D349 | Statins | Miscellany | -- | -- | -- | Under clinical trials | Details |