{"doi":"10.17615/d3je-1864","title":"Design, synthesis, and protein methyltransferase activity of a unique set of constrained amine containing compounds","abstract":"Epigenetic alterations relate to various human diseases, and developing inhibitors of Kme regulatory proteins is considered to be a new frontier for drug discovery. We were inspired by the known multicyclic ligands, UNC669 and UNC926, which are the first reported small molecule ligands for a methyl-lysine binding domain. We hypothesized that reducing the conformational flexibility of the key amine moiety of UNC669 would result in a unique set of ligands. Twenty-five novel compounds containing a fused bi- or tricyclic amine or a spirocyclic amine were designed and synthesized. To gauge the potential of these amine-containing compounds to interact with Kme regulatory proteins, the compounds were screened against a panel of 24 protein methyltransferases. Compound 13 was discovered as a novel scaffold that interacts with SETD8 and could serve as a starting point for the future development of PKMT inhibitors.","journal":"UNC Libraries","year":2020,"id":144036,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"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":612057,"name":"Kimberly D. Barnash","orcid":"0000-0002-0918-7188","position":1,"is_corresponding":false},{"id":392226,"name":"Stephen V. Frye","orcid":"0000-0002-2415-2215","position":2,"is_corresponding":false},{"id":612058,"name":"Xin Che","orcid":"0000-0002-5532-8287","position":3,"is_corresponding":false},{"id":612059,"name":"Hao Zhou","orcid":"0000-0002-3901-6582","position":4,"is_corresponding":false},{"id":361864,"name":"Peng Li","orcid":"0000-0003-2030-1807","position":5,"is_corresponding":false},{"id":612060,"name":"Guochen Bao","orcid":"0000-0001-5103-5009","position":6,"is_corresponding":false},{"id":540831,"name":"Lindsey I. James","orcid":"0000-0002-6034-7116","position":7,"is_corresponding":false},{"id":612061,"name":"Na Wang","orcid":"0000-0002-1703-1124","position":8,"is_corresponding":false},{"id":549030,"name":"Xu Bai","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","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":[]}