{"doi":"10.17615/qbdk-ee59","title":"Structure–Functional Selectivity Relationship Studies of β-Arrestin-Biased Dopamine D 2 Receptor Agonists","abstract":"Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and non-canonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side-effects of drugs. However, few such ligands have been created and very little purposeful attention has been devoted to studying what we term: ‘structure-functional selectivity relationships’ (SFSR). We recently disclosed the first β-arrestin-biased dopamine D2 receptor (D2R) agonists UNC9975 (44) and UNC9994 (36), which have robust in vivo antipsychotic drug-like activities. Here we report the first comprehensive SFSR studies focused on exploring four regions of the aripiprazole scaffold, which resulted in the discovery of these β-arrestin-biased D2R agonists. These studies provide a successful proof-of-concept for how functionally selective ligands can be discovered.","journal":"INDIGO (University of Illinois at Chicago)","year":2020,"id":117705,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"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":258568,"name":"William C. Wetsel","orcid":"0000-0002-3592-7397","position":1,"is_corresponding":false},{"id":525192,"name":"Jian Jin","orcid":"0000-0001-9685-3355","position":2,"is_corresponding":false},{"id":392226,"name":"Stephen V. Frye","orcid":"0000-0002-2415-2215","position":3,"is_corresponding":false},{"id":493749,"name":"Meng Chen","orcid":"0000-0002-2449-5904","position":4,"is_corresponding":false},{"id":504646,"name":"Maria F. Sassano","orcid":"0000-0003-1243-2962","position":5,"is_corresponding":false},{"id":549030,"name":"Xu Bai","orcid":null,"position":6,"is_corresponding":false},{"id":271306,"name":"Xin Chen","orcid":"0000-0002-5208-2154","position":7,"is_corresponding":false},{"id":225473,"name":"Bryan L. Roth","orcid":"0000-0002-0561-6520","position":8,"is_corresponding":false},{"id":548377,"name":"Lianyou Zheng","orcid":"0000-0002-7304-6734","position":9,"is_corresponding":false},{"id":548376,"name":"Vincent Setola","orcid":"0000-0002-9791-2270","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:54.951170Z","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":[]}