{"doi":"10.1101/2020.11.25.398586","title":"Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2","abstract":"ABSTRACT Increased activity of the lysine methyltrans-ferase NSD2 driven by translocation and activating mutations is associated with multiple myeloma and acute lymphoblastic leukemia, but no NSD2-targeting chemical probe has been reported to date. Here, we present the first antagonists that block the protein-protein interaction between the N-terminal PWWP domain of NSD2 and H3K36me2. Using virtual screening and experimental validation, we identified the small-molecule antagonist 3f , which binds to the NSD2-PWWP1 domain with a K d of 3.4 μM and abrogates histone H3K36me2 binding in cells. This study establishes an alternative approach to targeting NSD2 and provides a small-molecule antagonist that can be further optimized into a chemical probe to better understand the cellular function of this protein.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122393,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"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":563498,"name":"Yanli Liu","orcid":"0000-0003-0197-7617","position":1,"is_corresponding":false},{"id":277392,"name":"Magdalena M. Szewczyk","orcid":"0000-0001-9243-1630","position":2,"is_corresponding":false},{"id":564100,"name":"Naimee Mehta","orcid":null,"position":3,"is_corresponding":false},{"id":277394,"name":"Fengling Li","orcid":"0000-0002-7962-9033","position":4,"is_corresponding":false},{"id":277402,"name":"David McLeod","orcid":"0000-0003-4908-5554","position":5,"is_corresponding":false},{"id":563499,"name":"Carlos Zepeda‐Velázquez","orcid":"0000-0002-8130-2232","position":6,"is_corresponding":false},{"id":277399,"name":"David Dilworth","orcid":"0000-0001-5557-9476","position":7,"is_corresponding":false},{"id":564101,"name":"Ronan P. Hanley","orcid":null,"position":8,"is_corresponding":false},{"id":36729,"name":"Elisa Gibson","orcid":"0000-0002-7112-337X","position":9,"is_corresponding":false},{"id":36712,"name":"Peter J. Brown","orcid":"0000-0002-8454-0367","position":10,"is_corresponding":false},{"id":277405,"name":"Rima Al‐awar","orcid":"0000-0002-4185-055X","position":11,"is_corresponding":false},{"id":540831,"name":"Lindsey I. James","orcid":"0000-0002-6034-7116","position":12,"is_corresponding":false},{"id":84362,"name":"C.H. Arrowsmith","orcid":"0000-0002-4971-3250","position":13,"is_corresponding":false},{"id":277408,"name":"Dalia Baršytė-Lovejoy","orcid":"0000-0002-6560-9621","position":14,"is_corresponding":false},{"id":345478,"name":"Jinrong Min","orcid":"0000-0001-5210-3130","position":15,"is_corresponding":false},{"id":277407,"name":"Masoud Vedadi","orcid":"0000-0002-0574-0169","position":16,"is_corresponding":false},{"id":36797,"name":"Matthieu Schapira","orcid":"0000-0002-1047-3309","position":17,"is_corresponding":false},{"id":178002,"name":"Abdellah Allali‐Hassani","orcid":null,"position":18,"is_corresponding":false},{"id":563497,"name":"Renato Ferreira de Freitas","orcid":"0000-0001-6195-4236","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:51.076430Z","pmid":null,"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":[]}