{"doi":"10.1016/j.chembiol.2024.01.001","title":"Identification and characterization of a potent and selective HUNK inhibitor for treatment of HER2+ breast cancer","abstract":"Human epidermal growth factor receptor 2 (HER2)-targeted agents have proven to be effective, however, the development of resistance to these agents has become an obstacle in treating HER2+ breast cancer. Evidence implicates HUNK as an anti-cancer target for primary and resistant HER2+ breast cancers. In this study, a selective inhibitor of HUNK is characterized alongside a phosphorylation event in a downstream substrate of HUNK as a marker for HUNK activity in HER2+ breast cancer. Rubicon has been established as a substrate of HUNK that is phosphorylated at serine (S) 92. Findings indicate that HUNK-mediated phosphorylation of Rubicon at S92 promotes both autophagy and tumorigenesis in HER2/neu+ breast cancer. HUNK inhibition prevents Rubicon S92 phosphorylation in HER2/neu+ breast cancer models and inhibits tumorigenesis. This study characterizes a downstream phosphorylation event as a measure of HUNK activity and identifies a selective HUNK inhibitor that has meaningful efficacy toward HER2+ breast cancer.","journal":"Cell chemical biology","year":2024,"id":476280,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437390,"name":"Melissa Abt","orcid":"0000-0002-7107-7799","position":1,"is_corresponding":false},{"id":975404,"name":"Nicole Ramos-Solís","orcid":null,"position":2,"is_corresponding":false},{"id":748167,"name":"Neetu Dayal","orcid":"0000-0002-2705-7061","position":3,"is_corresponding":false},{"id":1079511,"name":"Elizabeth Larocque","orcid":"0009-0007-4550-9723","position":4,"is_corresponding":false},{"id":285575,"name":"Adrian L. Oblak","orcid":"0000-0003-1210-8791","position":5,"is_corresponding":false},{"id":748168,"name":"Herman O. Sintim","orcid":"0000-0002-2280-9359","position":6,"is_corresponding":false},{"id":437391,"name":"Elizabeth S. Yeh","orcid":"0009-0000-2940-3178","position":7,"is_corresponding":false},{"id":974925,"name":"Tinslee Dilday","orcid":"0000-0001-8427-4022","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:25.428435Z","pmid":"38307028","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":[]}