This excel spreadsheet contains the resultant data for over from inhibition assays with human Deiodinase 1 screened against the ToxCast Phase 1 chemical library and a few additional chemicals. Over 1800 chemicals were tested in total. It contains the list of chemicals tested and the median, minimum, and maximum inhibition for each chemical screened at 200 µM. Chemicals that gave greater than 50% inhibition were screened in concentration response mode, and the median, min, max inhibition at each concentration for those chemicals are included. Propylthiouracil was used in each plate as a positive control and the concentration-response data for those curves are also included. This dataset is associated with the following publication: Hornung, M., J. Korte, J. Olker, J. Denny, C. Knutsen, P. Hartig, M. Cardon, and S. Degitz. Screening the ToxCast Phase 1 chemical library for inhibition of deiodinase type 1 activity. TOXICOLOGICAL SCIENCES. Society of Toxicology, 162(2): 570-581, (2018).

Dataset for "Combining in vitro and in silico New Approach Methods to investigate type 3 iodothyronine deiodinase chemical inhibition across species". This dataset is associated with the following publication: Mayasich, S., M. Goldsmith, K. Mattingly, and C. Lalone. Combining In Vitro and In Silico New Approach Methods to Investigate Type 3 Iodothyronine Deiodinase Chemical Inhibition Across Species. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(5): 1032-1048, (2023).

High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using guaiacol as a substrate to confirm the activity profiles of putative TPO inhibitors. This effort represents the most extensive TPO inhibition screening campaign to date and illustrates a tiered screening approach that focuses resources, maximizes assay throughput, and reduces animal use. This dataset is associated with the following publication: Paul-Friedman, K., E.D. Watt , M.W. Hornung , J.M. Hedge , R.S. Judson , K.M. Crofton , K.A. Houck , and S.O. Simmons. (TOXICOLOGICAL SCIENCES) Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries. TOXICOLOGICAL SCIENCES. Society of Toxicology, 1-59, (2016).

This excel file contains the resultant data from a study on iodotyrosine deiodinase in the model amphibian species, Xenopus laevis. These data include: tadpole growth and development, thyroid hormones in plasma and glands, and expression of thyroid-relevant genes. The initial worksheet tab that provides metadata for each dataset included in the other worksheets that make up the file. This dataset is associated with the following publication: Olker, J., J. Haselman, P. Kosian, K. Donnay, J. Korte, C. Blanksma, M. Hornung, and S. Degitz. Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption in amphibians. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 166(2): 318-331, (2018).

Data pertaining to a NIS-expressing cell line, hNIS-HEK293T-EPA, and its screening capabilities for determining inhibitors of NIS-mediated iodide uptake. This dataset is associated with the following publication: Hallinger, D., A. Murr, A. Buckalew, S. Simmons, T. Stoker, and S. Laws. Development of a Screening Approach to Detect Thyroid Disrupting Chemicals that Inhibit the Human Sodium/Iodide Symporter (NIS). TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 66-78, (2017).

Data pertaining to a NIS-expressing cell line, FRTL-5 and it's screening capabilities for confirming inhibitors of NIS-mediated iodide uptake. This dataset is associated with the following publication: Buckalew, A., J. Wang, A. Murr, C. Deisenroth, W. Stewart, T. Stoker, and S. Laws. Evaluation of potential sodium-iodide symporter (NIS) inhibitors using a secondary Fischer rat thyroid follicular cell (FRTL-5) radioactive iodide uptake (RAIU) assay. Archives of Toxicology. Springer, New York, NY, USA, 94(3): 873-885, (2020).

This dataset contains in vitro and in vivo biochemical and apical (i.e., growth/development) data pertaining to iodotyrosine deiodinase inhibition in the African clawed frog (Xenopus laevis). This dataset is associated with the following publication: Haselman, J., J. Olker, P. Kosian, J. Korte, J. Denny, J. Tietge, M. Hornung, and S. Degitz. Characterization of the Mechanistic Linkages Between Iodothyronine Deiodinase Inhibition and Impaired Thyroid-Mediated Growth and Development in Xenopus Laevis Using Iopanoic Acid. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 139-149, (2022).

Dataset for 'A high throughput screening assay for human Thyroperoxidase inhibitors' by Hongyan Dong, et al., a collaboration work with primary authorship at Health Canada. Published in Toxicology in Vitro, Vol 101, 105946, Dec 2024; DOI https://doi.org/10.1016/j.tiv.2024.105946. Supplementary Data File 1: Examples of two solution plates and the resulting assay plate layouts for Single concentration phase. Supplementary Data File 2: The tcpl analyses of all multiple concentration phase data including plots of fitted models, estimates of log AC50 (ga), and hit call. Supplementary Data File 3: Supplementary Tables 1-5. For further data, please contact corresponding author Hongyan Dong at email Hongyan.Dong@hc-sc.gc.ca. This dataset is associated with the following publication: Dong, H., K. Friedman, A. Filiatreault, E. Thomson, and M. Wade. A high throughput screening assay for human Thyroperoxidase inhibitors. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 101: 105946, (2024).

Data on 1855 chemicals were generated during ToxCast Phases I and II and Tox21 screening using 11 AR-related in vitro assays to build a computational network model for AR pathway activity. This dataset is associated with the following publication: Kleinstreuer, N.C., P. Ceger, E. Watt, M. Martin, K. Houck, P. Browne, R. Thomas, W. Casey, D. Dix, D. Allen, S. Sakamuru, M. Xia, R. Huang, and R. Judson. (Chemical Research in Toxicology) Development and Validation of a Computational Model for Androgen Receptor Activity. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 30(4): 946-964, (2017).

ToxCast bioactivity data and model predictions for the estrogen receptor (ER) and androgen receptor (AR) pathways were obtained from the inks provided. This dataset is associated with the following publication: Lizarraga, L., J. Dean, J. Kaiser, S. Wesselkamper, J. Lambert, and J. Zhao. A Case Study on the Application of An Expert-driven Read-Across Approach in Support of Quantitative Risk Assessment of p,p’-Dichlorodiphenyldichloroethane. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 103: 301-313, (2019).