{"doi":"10.17615/dthk-as05","title":"Identification of novel small molecule Beclin 1 mimetics activating autophagy","abstract":"Anti-apoptotic proteins Bcl-2 and Bcl-xL could block autophagy by binding to Beclin 1 protein, an essential inducer of autophagy. Compounds mimicking Beclin 1 might be able to disrupt Bcl-xL/2-Beclin 1 interaction, free out Beclin 1, and thus trigger autophagy. In order to identify small molecule Beclin 1 mimetics, a fluorescence polarization-based high-throughput screening of 50,316 compounds was carried out with a Z' score of 0.82 ± 0.05, and an outcome of 58 hits. After the structure analysis, three acridine analogues were unveiled and confirmed using the fluorescence polarization assay and the surface plasmon resonance assay. Moreover, a set of 17 additional acridine analogues was prepared and tested. Compound 7 showed selectivity for Bcl-xL (KD = 6.5 μM) over Bcl-2 (KD = 160 μM) protein, and potent cytotoxicity (nanomolar scale) in PC-3, PC-3a and DU145 prostate cancer cells. Furthermore, induction of autophagy was also demonstrated in PC-3 and PC-3a cells treated with some acridine compounds by LC3 conversion immunoblotting and LC3 fluorescence microscopy. These Beclin 1 mimetics will be invaluable tools for developing novel autophagy inducers, better understanding the roles of autophagy in cancer, and will contribute to cancer therapy.","journal":"UNC Libraries","year":2022,"id":295881,"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":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":982589,"name":"P. Gao","orcid":null,"position":1,"is_corresponding":false},{"id":982590,"name":"S.J. Lewin","orcid":null,"position":2,"is_corresponding":false},{"id":535994,"name":"B. Sun","orcid":null,"position":3,"is_corresponding":false},{"id":10760,"name":"J. Yu","orcid":"0000-0002-6718-2975","position":4,"is_corresponding":false},{"id":945840,"name":"J. Aubé","orcid":null,"position":5,"is_corresponding":false},{"id":982591,"name":"XiaoPei Wu","orcid":null,"position":6,"is_corresponding":false},{"id":982097,"name":"Adheena Elsa Roy","orcid":"0009-0008-6000-9572","position":7,"is_corresponding":false},{"id":976225,"name":"S.A. Rogers","orcid":null,"position":8,"is_corresponding":false},{"id":982098,"name":"Lam Thi My Lan","orcid":"0009-0000-2655-2848","position":9,"is_corresponding":false},{"id":982099,"name":"Lingna Xu","orcid":"0009-0002-3310-5311","position":10,"is_corresponding":false},{"id":976193,"name":"J. Karanicolas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:31:12.531553Z","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":[]}