{"doi":"10.1126/sciadv.aaz8031","title":"Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment","abstract":"The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases, including prostate cancer, heart failure, and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes. Mechanistically, the inhibitor directly bound to the COUP-TFII ligand-binding domain and disrupted COUP-TFII interaction with transcription regulators, including FOXA1, thus repressing COUP-TFII activity on target gene regulation. Through blocking COUP-TFII's oncogenic activity in prostate cancer, the inhibitor efficiently exerted a potent antitumor effect in xenograft mouse models and patient-derived xenograft models. Our study identified a potent and specific COUP-TFII inhibitor that may be useful for the treatment of prostate cancer and possibly other diseases.","journal":"Science Advances","year":2020,"id":95294,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"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":474319,"name":"Chiang-Min Cheng","orcid":null,"position":1,"is_corresponding":false},{"id":473560,"name":"Jun Qin","orcid":"0000-0002-2263-128X","position":2,"is_corresponding":false},{"id":473561,"name":"Mafei Xu","orcid":"0000-0002-9064-7371","position":3,"is_corresponding":false},{"id":474320,"name":"Chung‐Yang Kao","orcid":null,"position":4,"is_corresponding":false},{"id":473562,"name":"Jingjing Shi","orcid":"0000-0001-5640-8687","position":5,"is_corresponding":false},{"id":474321,"name":"Erli You","orcid":null,"position":6,"is_corresponding":false},{"id":474322,"name":"Wanchun Gong","orcid":null,"position":7,"is_corresponding":false},{"id":474323,"name":"Laura Pedro Rosa","orcid":null,"position":8,"is_corresponding":false},{"id":474324,"name":"Peter Chase","orcid":null,"position":9,"is_corresponding":false},{"id":249872,"name":"Louis Scampavia","orcid":"0000-0002-7734-0105","position":10,"is_corresponding":false},{"id":474325,"name":"Franck Madoux","orcid":null,"position":11,"is_corresponding":false},{"id":249876,"name":"Timothy Spicer","orcid":"0000-0002-9080-4226","position":12,"is_corresponding":false},{"id":474326,"name":"Peter Hodder","orcid":null,"position":13,"is_corresponding":false},{"id":112933,"name":"H. Eric Xu","orcid":"0000-0002-6829-8144","position":14,"is_corresponding":false},{"id":245523,"name":"Sophia Y. Tsai","orcid":"0000-0002-5138-7159","position":15,"is_corresponding":false},{"id":245524,"name":"Ming‐Jer Tsai","orcid":"0000-0001-6287-908X","position":16,"is_corresponding":false},{"id":473559,"name":"Leiming Wang","orcid":"0000-0002-6602-473X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32494682","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":[]}