ArticleMolecular and cellular endocrinology2008
Complex actions of thyroid hormone receptor antagonist NH-3 on gene promoters in different cell lines.
Article in Molecular and cellular endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
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- Nuclear hormone receptors control fundamental processes of human fetal neurodevelopment: Basis for endocrine disruption assessment.Environment international · 2025Article
- Prophylactic administration of metformin alleviates withdrawal symptoms associated with heroin.Frontiers in pharmacology · 2025Article
- The Role of Maternal Thyroid Hormones in Avian Embryonic Development.Frontiers in endocrinology · 2019Review
- 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
- Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction.Bioorganic & medicinal chemistry letters · 2013Article
- Synthesis and evaluation of sulfonylnitrophenylthiazoles (SNPTs) as thyroid hormone receptor-coactivator interaction inhibitors.Journal of medicinal chemistry · 2012Article
- Similarities and differences between two modes of antagonism of the thyroid hormone receptor.ACS chemical biology · 2011Article
- Methylsulfonylnitrobenzoates, a new class of irreversible inhibitors of the interaction of the thyroid hormone receptor and its obligate coactivators that functionally antagonizes thyroid hormone.The Journal of biological chemistry · 2011Article
- Analysis of agonist and antagonist effects on thyroid hormone receptor conformation by hydrogen/deuterium exchange.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Identification of CCR4 and other essential thyroid hormone receptor co-activators by modified yeast synthetic genetic array analysis.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
It is desirable to obtain new antagonists for thyroid hormone receptors (TRs) and other nuclear receptors (NRs). We previously used X-ray structural models of TR ligand binding domains (LBDs) to design compounds, such as NH-3, that impair coactivator binding to activation function 2 (AF-2) and block thyroid hormone (triiodothyronine, T(3)) actions. However, TRs bind DNA and are transcriptionally active without ligand. Thus, NH-3 could modulate TR activity via effects on other coregulator interaction surfaces, such as activation function (AF-1) and corepressor binding sites. Here, we find that NH-3 blocks TR-LBD interactions with coactivators and corepressors and also inhibits activities of AF-1 and AF-2 in transfections. While NH-3 lacks detectable agonist activity at T(3)-activated genes in GC pituitary cells it nevertheless activates spot 14 (S14) in HTC liver cells with the latter effect accompanied by enhanced histone H4 acetylation and coactivator recruitment at the S14 promoter. Surprisingly, T(3) promotes corepressor recruitment to target promoters. NH-3 effects vary; we observe transient recruitment of N-CoR to S14 in GC cells and dismissal and rebinding of N-CoR to the same promoter in HTC cells. We propose that NH-3 will generally behave as an antagonist by blocking AF-1 and AF-2 but that complex effects on coregulator recruitment may result in partial/mixed agonist effects that are independent of blockade of T(3) binding in some contexts. These properties could ultimately be utilized in drug design and development of new selective TR modulators.
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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.