Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of cardiovascular and thermogenic effects
| Autor: | Kenneth S. Leonards, Steele Ronald Edward, Jong M. Wasvary, E.C. Yurachek, Zouhair F. Stephan, Chii Whei Hu, Robin Sharif, Thomas H. Hintze |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Thyroid Hormones medicine.medical_specialty Carcinoma Hepatocellular Hypercholesterolemia Drug Evaluation Preclinical Biology Binding Competitive Cardiovascular System Body Temperature Rats Sprague-Dawley chemistry.chemical_compound Dogs Oxygen Consumption In vivo Internal medicine Tumor Cells Cultured medicine Animals Myocyte Potency Cardiac Output Triglycerides Hypolipidemic Agents Cell Nucleus Cholesterol Anticholesteremic Agents Liver Neoplasms Glyoxylates Heart Metabolism Myocardial Contraction In vitro Rats Endocrinology medicine.anatomical_structure Animals Newborn Liver Receptors LDL chemistry Organ Specificity Cell culture Hepatocyte Triiodothyronine Safety Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 126:53-63 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/0021-9150(96)05893-5 |
| Popis: | A potent lipid-lowering thyromimetic (CGS 26214) devoid of cardiac and thermogenic activity was identified based on its ability to preferentially access and bind the nuclear fraction of hepatocytes over that of myocytes in culture. The difference in access achieved with CGS 26214 was at least 100-fold better for hepatocytes than for myocytes. This in vitro hepatoselectivity resulted in a compound with unprecedented in vivo lipid-lowering potency with a minimal effective dose of 1 microgram/kg in rats and dogs (approximately 25x that of L-T3). At the same time, CGS 26214 was free of any cardiovascular effects up to the highest dose tested of 25 mg/kg and 100 micrograms/kg in rats and dogs, respectively. |
| Databáze: | OpenAIRE |
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