Trial reportProceedings of the National Academy of Sciences of the United States of America2008
The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- Effects of Supra-Physiological Levothyroxine Dosages on Liver Parameters, Lipids and Lipoproteins in Healthy Volunteers: A Randomized Controlled Crossover Study.Scientific reports · 2017Trial
- Intake of partially defatted Brazil nut flour reduces serum cholesterol in hypercholesterolemic patients--a randomized controlled trial.Nutrition journal · 2015Trial
- Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans.Journal of lipid research · 2014Trial
- Resmetirom: The First FDA-Approved Drug for Metabolic Dysfunction-Associated Steatohepatitis (MASH) with a Perspective on Precision Medicine.Clinical drug investigation · 2025Review
- Lipid Hormones at the Intersection of Metabolic Imbalances and Endocrine Disorders.Current issues in molecular biology · 2025Review
- Hypothyroidism/subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease: advances in mechanism and treatment.Lipids in health and disease · 2025Review
- Drug discovery targeting thyroid hormone receptorActa pharmaceutica Sinica. B · 2025Review
- Targeting THR-β for MASLD: Mechanisms and Drug Development.Drug design, development and therapy · 2025Review
- Potential therapeutic strategies for MASH: from preclinical to clinical development.Life metabolism · 2024Review
- A new mechanism of thyroid hormone receptor β agonists ameliorating nonalcoholic steatohepatitis by inhibiting intestinal lipid absorption via remodeling bile acid profiles.Acta pharmacologica Sinica · 2024Article
- Molecular Dynamic Simulation To Reveal the Mechanism Underlying MGL-3196 Resistance to Thyroxine Receptor Beta.ACS omega · 2024Article
- Selective Agonists of Thyroid Hormone Receptor Beta: Promising Tools for the Treatment of Nonalcoholic Fatty Liver Disease.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Review
- Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression.iScience · 2023Article
- Receptor modulators associated with the hypothalamus -pituitary-thyroid axis.Frontiers in pharmacology · 2023Review
- Effects of Thyroid Hormones on Lipid Metabolism Pathologies in Non-Alcoholic Fatty Liver Disease.Biomedicines · 2022Review
- Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- [New development for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor beta].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.