ArticleProceedings of the National Academy of Sciences of the United States of America2003
Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 162 citations in OpenAlex.
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- Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells.Cancer cell · 2024Article
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- Daily exposure to low concentrations Tetrabromobisphenol A interferes with the thyroid hormone pathway in HepG2 cells.Fundamental research · 2023Article
- Allosteric regulation of CAD modulates de novo pyrimidine synthesis during the cell cycle.Nature metabolism · 2023Article
- Prioritizing Small Sets of Molecules for Synthesis through in-silico Tools: A Comparison of Common Ranking Methods.ChemMedChem · 2023Article
- Receptor modulators associated with the hypothalamus -pituitary-thyroid axis.Frontiers in pharmacology · 2023Review
- Investigation of NH3 as a selective thyroid hormone receptor modulator in larval zebrafish (Danio rerio).Neurotoxicology · 2021Article
- Data-Driven Strategies for Accelerated Materials Design.Accounts of chemical research · 2021Article
- The RNA-Binding Proteins SRP14 and HMGB3 Control HIV-1 Tat mRNA Processing and Translation During HIV-1 Latency.Frontiers in genetics · 2021Article
- Thyroid Hormone Signaling in Embryonic Stem Cells: Crosstalk with the Retinoic Acid Pathway.International journal of molecular sciences · 2020Article
- Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders.Frontiers in medicine · 2020Review
- Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library.Environmental health perspectives · 2019Article
- Thyroid receptor antagonism as a contributory mechanism for adipogenesis induced by environmental mixtures in 3T3-L1 cells.The Science of the total environment · 2019Article
- Classification of thyroid hormone receptor agonists and antagonists using statistical learning approaches.Molecular diversity · 2019Article
- Dioxin Exposure Alters Molecular and Morphological Responses to Thyroid Hormone in Xenopus laevis Cultured Cells and Prometamorphic Tadpoles.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Treatment of hyperthyroidism, a common clinical condition that can have serious manifestations in the elderly, has remained essentially unchanged for >30 years. Directly antagonizing the effect of the thyroid hormone at the receptor level may be a significant improvement for the treatment of hyperthyroid patients. We built a computer model of the thyroid hormone receptor (TR) ligand-binding domain in its predicted antagonist-bound conformation and used a virtual screening algorithm to select 100 TR antagonist candidates out of a library of >250,000 compounds. We were able to obtain 75 of the compounds selected in silico and studied their ability to act as antagonists by using cultured cells that express TR. Fourteen of these compounds were found to antagonize the effect of T3 on TR with IC50s ranging from 1.5 to 30 microM. A small virtual library of compounds, derived from the highest affinity antagonist (1-850) that could be rapidly synthesized, was generated. A second round of virtual screening identified new compounds with predicted increased antagonist activity. These second generation compounds were synthesized, and their ability to act as TR antagonists was confirmed by transfection and receptor binding experiments. The extreme structural diversity of the antagonist compounds shows how receptor-based virtual screening can identify diverse chemistries that comply with the structural rules of TR antagonism.
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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.