{"doi":"10.1002/cbic.202100118","title":"A Potent, Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation","abstract":"Abstract Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N‐terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K d of 80 nM and displays 24‐1000‐fold selectivity for CBX2 ChD over other CBX paralogs in vitro . SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.","journal":"ChemBioChem","year":2021,"id":154416,"datarank":1.4759335330159868,"base_score":4.1588830833596715,"endowment":4.1588830833596715,"self_citation_contribution":0.6238324625039509,"citation_network_contribution":0.852101070512036,"self_endowment_contribution":0.6238324625039509,"citer_contribution":0.852101070512036,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":48,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":303985,"name":"Aktan Alpsoy","orcid":"0000-0002-8940-8277","position":1,"is_corresponding":false},{"id":655875,"name":"Surbhi Sood","orcid":null,"position":2,"is_corresponding":false},{"id":654658,"name":"Sandra C. Ordonez-Rubiano","orcid":"0000-0001-7967-5024","position":3,"is_corresponding":false},{"id":303987,"name":"Alisha Dhiman","orcid":"0000-0002-4395-9292","position":4,"is_corresponding":false},{"id":655876,"name":"Yixing Sun","orcid":null,"position":5,"is_corresponding":false},{"id":655877,"name":"Guanming Jiao","orcid":null,"position":6,"is_corresponding":false},{"id":654659,"name":"Casey J. Krusemark","orcid":"0000-0003-2964-3520","position":7,"is_corresponding":false},{"id":303990,"name":"Emily C. Dykhuizen","orcid":"0000-0003-3072-1469","position":8,"is_corresponding":false},{"id":654657,"name":"Sijie Wang","orcid":"0009-0004-9098-0993","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:54.469024Z","pmid":"33950564","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":[]}