ArticleFrontiers in endocrinology2016
The "TSH Receptor Glo Assay" - A High-Throughput Detection System for Thyroid Stimulation.
Article in Frontiers in endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Brief Report - Monoclonal Antibodies Illustrate the Difficulties in Measuring Blocking TSH Receptor Antibodies.Frontiers in endocrinology · 2022Article
- Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- The Human TSHβ Subunit Proteins and Their Binding Sites on the TSH Receptor Using Molecular Dynamics Simulation.Endocrinology · 2020Article
- Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves' disease.Journal of autoimmunity · 2020Article
- TSHR Signaling Stimulates Proliferation Through PI3K/Akt and Induction of miR-146a and miR-155 in Thyroid Eye Disease Orbital Fibroblasts.Investigative ophthalmology & visual science · 2019Article
- A Modifying Autoantigen in Graves' Disease.Endocrinology · 2019Article
- Antigenic "Hot- Spots" on the TSH Receptor Hinge Region.Frontiers in endocrinology · 2018Article
- Reversing thyroid-hormone-mediated repression of a HSV-1 promoter via computationally guided mutagenesis.Journal of cell science · 2017Article
- TSH Receptor Signaling Abrogation by a Novel Small Molecule.Frontiers in endocrinology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTo identify novel small molecules against the TSH receptor, we developed a sensitive transcription-based luciferase high-throughput screening (HTS) system named the TSHR-Glo Assay (TSHR-Glo).
methodsThis assay uses double-transfected Chinese hamster ovary cells stably expressing the human TSHR and a cAMP-response element (CRE) construct fused to an improved luciferase reporter gene.
resultsThe assay was highly responsive toward TSH in a dose-dependent manner with a TSH sensitivity of 10(-10)M (10 ± 1.12 μU/ml) and thyroid-stimulating antibodies, a hallmark of Graves' disease, could also be detected. The assay was validated against the standard indicator of HTS performance - the Z-factor (Z') - producing a score of 0.895. Using the TSHR-Glo assay, we screened 48,224 compounds from a diverse chemical library in duplicate plates at a fixed dose of 17 μM. Twenty molecules with the greatest activity out of 62 molecules that were identified by this technique were subsequently screened against the parent luciferase stable cell line in order to eliminate false positive stimulators.
conclusionUsing this approach, we were able to identify specific agonists against the TSH receptor leading to the characterization of several TSH agonist molecules. Hence, the TSHR-Glo assay was a one-step cell-based HTS assay, which was successful in the discovery of novel small molecular agonists and for the detection of stimulating antibodies to the TSH receptor.
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