Dataset for the publication "Expanded High-Throughput Screening and Chemotype-Enrichment Analysis of the Phase II:e1k ToxCast Library for Human Sodium-Iodide Symporter (NIS) Inhibition". https://doi.org/10.1007/s00204-021-03006-2 Dataset1 contains data for figures. Dataset2 contains all supplemental tables data. This dataset is associated with the following publication: Wang, J., A. Richard, A. Murr, A. Buckalew, R. Lougee, M.A. Shobair, D. Hallinger, S. Laws, and T. Stoker. Expanded High-Throughput Screening and Chemotype-Enrichment Analysis of the Phase II:e1k ToxCast Library for Human Sodium-Iodide Symporter (NIS) Inhibition. Archives of Toxicology. Springer, New York, NY, USA, 95(5): 1723-1737, (2021).

Dataset for the publication "Expanded High-Throughput Screening and Chemotype-Enrichment Analysis of the Phase II:e1k ToxCast Library for Human Sodium-Iodide Symporter (NIS) Inhibition". https://doi.org/10.1007/s00204-021-03006-2 Dataset1 contains data for figures. Dataset2 contains all supplemental tables data. This dataset is associated with the following publication: Wang, J., A. Richard, A. Murr, A. Buckalew, R. Lougee, M.A. Shobair, D. Hallinger, S. Laws, and T. Stoker. Expanded High-Throughput Screening and Chemotype-Enrichment Analysis of the Phase II:e1k ToxCast Library for Human Sodium-Iodide Symporter (NIS) Inhibition. Archives of Toxicology. Springer, New York, NY, USA, 95(5): 1723-1737, (2021).

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).

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 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).

The excel spreadsheet contains the resultant data from an assay for chemical inhibition of human Iodotyrosine Deiodinase (IYD) enzyme activity screened against the ToxCast Phase 1_v2, Phase 2, and e1k chemical libraries, as well as a few additional target chemicals from ToxCast Phase 3 library or used in assay development. Over 1,800 chemicals were tested in total. This data set includes the list of chemicals tested and the median, minimum, and maximum inhibition produced by each chemical when screened at target high concentration of 200 µM. 154 chemicals were further tested in concentration response, and the median, minimum, and maximum inhibition produced at each concentration for those chemicals are included. A model inhibitor (3-Nitro-L-Tyrosine) was included on each plate as a positive control, with concentration response data for those curves also included in the data set. This dataset is associated with the following publication: Olker, J., J. Korte, J. Denny, J. Haselman, P. Hartig, M. Cardon, M. Hornung, and S. Degitz. In Vitro Screening for Chemical Inhibition of the Iodide Recycling Enzyme, Iodotyrosine Deiodinase. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, 71: 105073, (2021).

The excel spreadsheet contains the resultant data from an assay for chemical inhibition of human Iodotyrosine Deiodinase (IYD) enzyme activity screened against the ToxCast Phase 1_v2, Phase 2, and e1k chemical libraries, as well as a few additional target chemicals from ToxCast Phase 3 library or used in assay development. Over 1,800 chemicals were tested in total. This data set includes the list of chemicals tested and the median, minimum, and maximum inhibition produced by each chemical when screened at target high concentration of 200 µM. 154 chemicals were further tested in concentration response, and the median, minimum, and maximum inhibition produced at each concentration for those chemicals are included. A model inhibitor (3-Nitro-L-Tyrosine) was included on each plate as a positive control, with concentration response data for those curves also included in the data set. This dataset is associated with the following publication: Olker, J., J. Korte, J. Denny, J. Haselman, P. Hartig, M. Cardon, M. Hornung, and S. Degitz. In Vitro Screening for Chemical Inhibition of the Iodide Recycling Enzyme, Iodotyrosine Deiodinase. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, 71: 105073, (2021).

The Tox21 chemical library (8,305 unique structures) was screened in a quantitative high-throughput, cell-based reporter gene assay for TR agonist or antagonist activity. Active compounds were further characterized using additional orthogonal assays, including mammalian one-hybrid assays, coactivator recruitment assays, and a high-throughput, fluorescent imaging, nuclear receptor translocation assay. Results for the library are available at https://tripod.nih.gov/tox21/samples. This dataset is associated with the following publication: Paul-Friedman, K., M. Martin, K. Crofton, C. Hsu, S. Sakamuru, J. Zhao, M. Xia, R. Huang, D. Stevreva, V. Soni, L. Varticovski, R. Raziuddin, G. Hager, and K. Houck. Limited chemical structural diversity found to modulate thyroid hormone receptor in the Tox21 chemical library. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA, 127(9): 1-16, (2019).

The Tox21 chemical library (8,305 unique structures) was screened in a quantitative high-throughput, cell-based reporter gene assay for TR agonist or antagonist activity. Active compounds were further characterized using additional orthogonal assays, including mammalian one-hybrid assays, coactivator recruitment assays, and a high-throughput, fluorescent imaging, nuclear receptor translocation assay. Results for the library are available at https://tripod.nih.gov/tox21/samples. This dataset is associated with the following publication: Paul-Friedman, K., M. Martin, K. Crofton, C. Hsu, S. Sakamuru, J. Zhao, M. Xia, R. Huang, D. Stevreva, V. Soni, L. Varticovski, R. Raziuddin, G. Hager, and K. Houck. Limited chemical structural diversity found to modulate thyroid hormone receptor in the Tox21 chemical library. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA, 127(9): 1-16, (2019).

These excel spreadsheets contains the resultant data from inhibition assays with human Iodothyronine Deiodinase Types 1, 2, and 3 screened against the ToxCast Phase 1_v2, Phase 2, and e1k chemical libraries, as well as a few additional chemicals used in assay development. Over 1,800 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. A model inhibitor (propylthiouracil or xanthohumol) 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: Olker, J., J. Korte, J. Denny, P. Hartig, M. Cardon, C. Knutsen, P. Kent, J. Christensen, S. Degitz, and M. Hornung. Screening the ToxCast Phase 1, Phase 2, and e1k Chemical Libraries for Inhibitors of Iodothyronine Deiodinases. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 168(2): 430-442, (2019).