{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wei Z"],"funding":["NIEHS NIH HHS"],"pagination":["1321857"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10933113"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6"],"pubmed_abstract":["<b>Introduction:</b> Skin sensitization, which leads to allergic contact dermatitis, is a key toxicological endpoint with high occupational and consumer prevalence. This study optimized several <i>in vitro</i> assays listed in OECD skin sensitization test guidelines for use on a quantitative high-throughput screening (qHTS) platform and performed <i>in silico</i> model predictions to assess the skin sensitization potential of prioritized compounds from the Tox21 10K compound library. <b>Methods:</b> First, we screened the entire Tox21 10K compound library using a qHTS KeratinoSens<sup>TM</sup> (KS) assay and built a quantitative structure-activity relationship (QSAR) model based on the KS results. From the qHTS KS screening results, we prioritized 288 compounds to cover a wide range of structural chemotypes and tested them in the solid phase extraction-tandem mass spectrometry (SPE-MS/MS) direct peptide reactivity assay (DPRA), IL-8 homogeneous time-resolved fluorescence (HTRF) assay, CD86 and CD54 surface expression in THP1 cells, and predicted <i>in silico</i> sensitization potential using the OECD QSAR Toolbox (v4.5). <b>Results:</b> Interpreting tiered qHTS datasets using a defined approach showed the effectiveness and efficiency of <i>in vitro</i> methods. We selected structural chemotypes to present this diverse chemical collection and to explore previously unidentified structural contributions to sensitization potential. <b>Discussion:</b> Here, we provide a skin sensitization dataset of unprecedented size, along with associated tools, and analysis designed to support chemical assessments."],"journal":["Frontiers in toxicology"],"pubmed_title":["Use of &lt;i&gt;in vitro&lt;/i&gt; methods combined with &lt;i&gt;in silico&lt;/i&gt; analysis to identify potential skin sensitizers in the Tox21 10K compound library."],"pmcid":["PMC10933113"],"funding_grant_id":["HHSN273201500010C"],"pubmed_authors":["Fang Y","Strickland J","Kleinstreuer NC","Xia M","Simeonov A","Xu T","Zhang L","Tao D","Wei Z","Huang R"],"additional_accession":[]},"is_claimable":false,"name":"Use of &lt;i&gt;in vitro&lt;/i&gt; methods combined with &lt;i&gt;in silico&lt;/i&gt; analysis to identify potential skin sensitizers in the Tox21 10K compound library.","description":"<b>Introduction:</b> Skin sensitization, which leads to allergic contact dermatitis, is a key toxicological endpoint with high occupational and consumer prevalence. This study optimized several <i>in vitro</i> assays listed in OECD skin sensitization test guidelines for use on a quantitative high-throughput screening (qHTS) platform and performed <i>in silico</i> model predictions to assess the skin sensitization potential of prioritized compounds from the Tox21 10K compound library. <b>Methods:</b> First, we screened the entire Tox21 10K compound library using a qHTS KeratinoSens<sup>TM</sup> (KS) assay and built a quantitative structure-activity relationship (QSAR) model based on the KS results. From the qHTS KS screening results, we prioritized 288 compounds to cover a wide range of structural chemotypes and tested them in the solid phase extraction-tandem mass spectrometry (SPE-MS/MS) direct peptide reactivity assay (DPRA), IL-8 homogeneous time-resolved fluorescence (HTRF) assay, CD86 and CD54 surface expression in THP1 cells, and predicted <i>in silico</i> sensitization potential using the OECD QSAR Toolbox (v4.5). <b>Results:</b> Interpreting tiered qHTS datasets using a defined approach showed the effectiveness and efficiency of <i>in vitro</i> methods. We selected structural chemotypes to present this diverse chemical collection and to explore previously unidentified structural contributions to sensitization potential. <b>Discussion:</b> Here, we provide a skin sensitization dataset of unprecedented size, along with associated tools, and analysis designed to support chemical assessments.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-25T03:17:55.307Z","creation":"2025-02-19T04:41:24.384Z"},"accession":"S-EPMC10933113","cross_references":{"pubmed":["38482198"],"doi":["10.3389/ftox.2024.1321857"]}}