{"doi":"10.1021/acschembio.0c00124","title":"Cell-Based Ligand Discovery for the ENL YEATS Domain","abstract":"-regulatory elements upon binding of its YEATS domain-a chromatin reader module-to acylated lysine side chains. Discovery chemistry for the ENL YEATS domain is highly motivated by its significance in acute leukemia pathophysiology, but cell-based assays able to support large-scale screening or hit validation efforts do not presently exist. Here, we report on the discovery of a target engagement assay that allows for high-throughput ligand discovery in living cells. This assay is based on the cellular thermal shift assay (CETSA) but does not require exposing cells to elevated temperatures, as small-molecule ligands are able to stabilize the ENL YEATS domain at 37 °C. By eliminating temperature shifts, we developed a simplified target engagement assay that requires just two steps: drug treatment and luminescence detection. To demonstrate its value for higher throughput applications, we miniaturized the assay to a 1536-well format and screened 37 120 small molecules, ultimately identifying an acyl-lysine-competitive ENL/AF9 YEATS domain inhibitor.","journal":"ACS Chemical Biology","year":2020,"id":94156,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469464,"name":"Natalia Milosevich","orcid":"0000-0001-5708-6907","position":1,"is_corresponding":false},{"id":329380,"name":"Emily Chen","orcid":"0000-0001-7169-8192","position":2,"is_corresponding":false},{"id":116743,"name":"Timothy Bishop","orcid":"0000-0002-0321-7809","position":3,"is_corresponding":false},{"id":469465,"name":"Justin Wang","orcid":"0009-0000-4224-9443","position":4,"is_corresponding":false},{"id":469466,"name":"Yuxiang Zhang","orcid":"0000-0002-5110-5684","position":5,"is_corresponding":false},{"id":470532,"name":"Christopher J. Ackerman","orcid":null,"position":6,"is_corresponding":false},{"id":469467,"name":"Eric Hampton","orcid":"0000-0003-3104-3612","position":7,"is_corresponding":false},{"id":469468,"name":"Travis S. Young","orcid":"0000-0001-8562-5736","position":8,"is_corresponding":false},{"id":107914,"name":"Mitchell Hull","orcid":"0000-0002-9364-1901","position":9,"is_corresponding":false},{"id":236419,"name":"Benjamin F. Cravatt","orcid":"0000-0001-5330-3492","position":10,"is_corresponding":false},{"id":116744,"name":"Michael A. Erb","orcid":"0000-0001-9993-3481","position":11,"is_corresponding":false},{"id":469463,"name":"Joshua N. Asiaban","orcid":"0000-0001-6425-012X","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"32176478","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}