{"doi":"10.1126/sciadv.ado1432","title":"A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression","abstract":"The histone acylation reader eleven-nineteen leukemia (ENL) plays a pivotal role in sustaining oncogenesis in acute leukemias, particularly in mixed-lineage leukemia –rearranged ( MLL -r) leukemia. ENL relies on its reader domain to recognize histone lysine acylation promoting oncogenic gene expression and leukemia progression. Here, we report the development of MS41, a highly potent and selective von Hippel–Lindau–recruiting ENL degrader that effectively inhibits the growth of ENL-dependent leukemia cells. MS41-induced ENL degradation reduces the chromatin occupancy of ENL-associated transcription elongation machinery, resulting in the suppression of key oncogenic gene expression programs and the activation of differentiation genes. MS41 is well-tolerated in vivo and substantially suppresses leukemia progression in a xenograft mouse model of MLL-r leukemia. Notably, MS41 also induces the degradation of mutant ENL proteins identified in Wilms’ tumors. Our findings emphasize the therapeutic potential of pharmacological ENL degradation for treating ENL-dependent cancers, making MS41 not only a valuable chemical probe but also potential anticancer therapeutic for further development.","journal":"Science Advances","year":2024,"id":427881,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337231,"name":"Lihuai Qin","orcid":"0000-0001-5795-5703","position":1,"is_corresponding":false},{"id":385878,"name":"Hongwen Xuan","orcid":"0000-0002-4095-6352","position":2,"is_corresponding":false},{"id":994164,"name":"Kaixiu Luo","orcid":"0000-0002-7910-7454","position":3,"is_corresponding":false},{"id":1066987,"name":"Mengying Huang","orcid":"0000-0002-9719-4619","position":4,"is_corresponding":false},{"id":57593,"name":"Ling Xie","orcid":"0000-0002-3577-8774","position":5,"is_corresponding":false},{"id":1228591,"name":"Yangzhou Su","orcid":"0009-0002-7820-7100","position":6,"is_corresponding":false},{"id":1067347,"name":"Longxia Xu","orcid":null,"position":7,"is_corresponding":false},{"id":1228592,"name":"Josiah Harsh","orcid":"0009-0000-3989-1697","position":8,"is_corresponding":false},{"id":780590,"name":"Brandon Dale","orcid":"0000-0003-0203-2105","position":9,"is_corresponding":false},{"id":329463,"name":"Xiaobing Shi","orcid":"0000-0001-5242-8189","position":10,"is_corresponding":false},{"id":11742,"name":"Xian Chen","orcid":"0000-0002-8358-1247","position":11,"is_corresponding":false},{"id":228876,"name":"H. Ümit Kanıskan","orcid":"0000-0001-5327-832X","position":12,"is_corresponding":false},{"id":228877,"name":"Jian Jin","orcid":"0000-0002-2387-3862","position":13,"is_corresponding":false},{"id":733932,"name":"Hong Wen","orcid":"0000-0001-8739-4572","position":14,"is_corresponding":false},{"id":520607,"name":"Zhaoyu Xue","orcid":"0000-0001-7288-8780","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:58:52.576447Z","pmid":"39196923","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":[]}