ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Screening the ToxCast Phase 1 Chemical Library for Inhibition of Deiodinase Type 1 Activity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
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- Machine Learning and Large Language Models for Modeling Complex Toxicity Pathways and Predicting Steroidogenesis.Environmental science & technology · 2025Article
- Advancing in vitro assessment of iodide uptake inhibition: integrating a novel biotransformation pretreatment step.Archives of toxicology · 2025Article
- Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Screening the ToxCast Chemical Libraries for Binding to Transthyretin.Chemical research in toxicology · 2024Article
- In Vitro Screening for ToxCast Chemicals Binding to Thyroxine-Binding Globulin.Chemical research in toxicology · 2024Article
- Seminar: Functional Exposomics and Mechanisms of Toxicity-Insights from Model Systems and NAMs.Environmental health perspectives · 2024Review
- Technical evaluation and standardization of the human thyroid microtissue assay.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- In vitro screening of per- and polyfluorinated substances (PFAS) for interference with seven thyroid hormone system targets across nine assays.Toxicology in vitro : an international journal published in association with BIBRA · 2024Article
- Characterization of a human thyroid microtissue model for testing thyroid disrupting chemicals.Frontiers in toxicology · 2024Article
- A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment.Open research Europe · 2024Review
- Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo.Regulatory toxicology and pharmacology : RTP · 2023Review
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians.Environmental toxicology and chemistry · 2023Review
- High-Throughput Screening of ToxCast PFAS Chemical Library for Potential Inhibitors of the Human Sodium Iodide Symporter.Chemical research in toxicology · 2023Article
- Phenol and Phthalate Effects on Thyroid Hormone Levels during Pregnancy: Relying onEnvironmental health perspectives · 2022Article
- Advances in computational methods along the exposure to toxicological response paradigm.Toxicology and applied pharmacology · 2022Article
- Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase.Aquatic toxicology (Amsterdam, Netherlands) · 2022Article
- Characterization of the Mechanistic Linkages Between Iodothyronine Deiodinase Inhibition and Impaired Thyroid-Mediated Growth and Development in Xenopus laevis Using Iopanoic Acid.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Tentative Application of a Streamlined Protocol to Determine Organ-Specific Regulations of Deiodinase 1 and Dehalogenase Activities as Readouts of the Hypothalamus-Pituitary-Thyroid-Periphery-Axis.Frontiers in toxicology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Thyroid hormone (TH) homeostasis is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism, and elimination, to maintain proper TH signaling. Deiodinase enzymes catalyze iodide release from THs to interconvert THs between active and inactive forms, and are integral to hormone metabolism. The activity of deiodinases has been identified as an important endpoint to include in the context of screening chemicals for TH disruption. To begin to address the potential for chemicals to inhibit these enzymes an adenovirus expression system was used to produce human deiodinase type 1 (DIO1) enzyme, established robust assay parameters for nonradioactive determination of iodide release by the Sandell-Kolthoff method, and employed a 96-well plate format for screening chemical libraries. An initial set of 18 chemicals was used to establish the assay, along with the known DIO1 inhibitor 6-propylthiouracil as a positive control. An additional 292 unique chemicals from the EPA's ToxCast phase 1_v2 chemical library were screened. Chemicals were initially screened at a single high concentration of 200 µM to identify potential DIO1 inhibitors. There were 50 chemicals, or 17% of the TCp1_v2 chemicals tested, that produced >20% inhibition of DIO1 activity. Eighteen of these inhibited DIO1 activity >50% and were further tested in concentration-response mode to determine IC50s. This work presents an initial effort toward identifying chemicals with potential for affecting THs via inhibition of deiodinases and sets the foundation for further testing of large chemical libraries against DIO1 and the other deiodinase enzymes involved in TH function.
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Registered trials
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