{"doi":"10.3389/fphar.2023.1137783","title":"Urolithin A analog inhibits castration-resistant prostate cancer by targeting the androgen receptor and its variant, androgen receptor-variant 7","abstract":"We investigated the efficacy of a small molecule ASR-600, an analog of Urolithin A (Uro A), on blocking androgen receptor (AR) and its splice variant AR-variant 7 (AR-V7) signaling in castration-resistant prostate cancer (CRPC). ASR-600 effectively suppressed the growth of AR + CRPC cells by inhibiting AR and AR-V7 expressions; no effect was seen in AR − CRPC and normal prostate epithelial cells. Biomolecular interaction assays revealed ASR-600 binds to the N-terminal domain of AR, which was further confirmed by immunoblot and subcellular localization studies. Molecular studies suggested that ASR-600 promotes the ubiquitination of AR and AR-V7 resulting in the inhibition of AR signaling. Microsomal and plasma stability studies suggest that ASR-600 is stable, and its oral administration inhibits tumor growth in CRPC xenografted castrated and non-castrated mice. In conclusion, our data suggest that ASR-600 enhances AR ubiquitination in both AR + and AR-V7 CRPC cells and inhibits their growth in vitro and in vivo models.","journal":"Frontiers in Pharmacology","year":2023,"id":359114,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":249224,"name":"Ashish Tyagi","orcid":"0000-0003-2909-5755","position":1,"is_corresponding":false},{"id":910568,"name":"Uttara Saran","orcid":"0000-0002-3705-5123","position":2,"is_corresponding":false},{"id":519123,"name":"Venkatesh Kolluru","orcid":"0000-0002-7318-2090","position":3,"is_corresponding":false},{"id":497371,"name":"Becca V. Baby","orcid":"0000-0002-2631-8426","position":4,"is_corresponding":false},{"id":512915,"name":"Venkat R. Chirasani","orcid":"0000-0003-1416-0438","position":5,"is_corresponding":false},{"id":149320,"name":"Nikolay V. Dokholyan","orcid":"0000-0002-8225-4025","position":6,"is_corresponding":false},{"id":1110177,"name":"Jyh Ming Lin","orcid":null,"position":7,"is_corresponding":false},{"id":865866,"name":"Amandeep Singh","orcid":"0000-0002-0210-5012","position":8,"is_corresponding":false},{"id":249225,"name":"Arun Sharma","orcid":"0000-0002-7679-7779","position":9,"is_corresponding":false},{"id":519125,"name":"Murali K. Ankem","orcid":"0000-0002-8098-979X","position":10,"is_corresponding":false},{"id":249226,"name":"Chendil Damodaran","orcid":"0000-0002-9902-7101","position":11,"is_corresponding":false},{"id":519122,"name":"Balaji Chandrasekaran","orcid":"0000-0001-7786-5385","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:52.889556Z","pmid":"36937838","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":[]}