Development of a HT-ATACseq assay to identify epigenetic regulators of Ewing Sarcoma cancer cells (Chemical Biology Consortium/NCI Experimental Therapeutics Collaboration)

National Center For Advancing Translational Sciences

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Abstract

During this period, the project team has completed screening of the NCATS diversity collections (>27,000 compounds) and has made significant progress screening the Chemical Library Consortia Curia collection (>91,000 compounds screened, ~50,000 remain) using a high-throughput screening platform capable of measuring dynamic states of chromatin accessibility in Ewing sarcoma cells using an enzyme-based approach (Assay for Transpose-Accessible Chromatin (ATAC). In total, we have screened ~130,000 compounds, hits have been identified and clustered based on mechanism of action. Currently, hits are being cherry-picked and tested for confirmation in dose-response. Next steps will include expansion of hit chemotypes and testing of compounds in orthogonal assays.