ArticleEndocrinology2014
A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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.
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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.
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Who cites it
48 citing papers in PubMed, 109 citations in OpenAlex.
- The evolving therapeutic landscape of Graves' disease in adults: present and future.European thyroid journal · 2025Review
- 2'-O-Galloylhyperin Prevents Tissue Remodeling in Thyroid Eye Disease: Prospects as a Thyrotropin Receptor Antagonist.The Journal of clinical endocrinology and metabolism · 2025Article
- Radioiodine Exhalation Following Oral I-131 Administration in a Mouse Model.Biomedicines · 2025Article
- Graves' Disease: Is It Time for Targeted Therapy? A Narrative Review.Medicina (Kaunas, Lithuania) · 2025Review
- Butyrate Ameliorates Graves' Orbitopathy Through Regulating Orbital Fibroblast Phenotypes and Gut Microbiota.Investigative ophthalmology & visual science · 2025Article
- Effect of a Low-Molecular-Weight Allosteric Agonist of the Thyroid-Stimulating Hormone Receptor on Basal and Thyroliberin-Stimulated Activity of Thyroid System in Diabetic Rats.International journal of molecular sciences · 2025Article
- Targeted immunotherapies for Graves' thyroidal & orbital diseases.Frontiers in immunology · 2025Review
- Teprotumumab in the management of thyroid eye disease mechanistic insights and adverse reactions: a comprehensive review.Frontiers in endocrinology · 2025Review
- Graves disease: latest understanding of pathogenesis and treatment options.Nature reviews. Endocrinology · 2024Review
- An Orally Efficacious Thyrotropin Receptor Ligand Inhibits Growth and Metastatic Activity of Thyroid Cancers.The Journal of clinical endocrinology and metabolism · 2024Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells.International journal of molecular sciences · 2023Article
- Current and promising therapies based on the pathogenesis of Graves' ophthalmopathy.Frontiers in pharmacology · 2023Review
- Receptor modulators associated with the hypothalamus -pituitary-thyroid axis.Frontiers in pharmacology · 2023Review
- Current concepts regarding Graves' orbitopathy.Journal of internal medicine · 2022Review
- 2021 update on thyroid-associated ophthalmopathy.Journal of endocrinological investigation · 2022Review
- New Therapeutic Horizon of Graves' Hyperthyroidism: Treatment Regimens Based on Immunology and Ingredients From Traditional Chinese Medicine.Frontiers in pharmacology · 2022Review
- Implications of an Improved Model of the TSH Receptor Transmembrane Domain (TSHR-TMD-TRIO).Endocrinology · 2021Article
- Thyroid Eye Disease: Navigating the New Treatment Landscape.Journal of the Endocrine Society · 2021Article
- Modulating TSH Receptor Signaling for Therapeutic Benefit.European thyroid journal · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.
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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.