{"doi":"10.1002/ctm2.627","title":"Discovery and characterization of potent And‐1 inhibitors for cancer treatment","abstract":"Acidic nucleoplasmic DNA-binding protein 1 (And-1), an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues. Although multiple independent studies have elucidated And-1 as a promising target gene for cancer therapy, an And-1 inhibitor has yet to be identified. Using an And-1 luciferase reporter assay to screen the Library of Pharmacologically Active Compounds (LOPAC) in a high throughput screening (HTS) platform, and then further screen the compound analog collection, we identified two potent And-1 inhibitors, bazedoxifene acetate (BZA) and an uncharacterized compound [(E)-5-(3,4-dichlorostyryl)benzo[c][1,2]oxaborol-1(3H)-ol] (CH3), which specifically inhibit And-1 by promoting its degradation. Specifically, through direct interaction with And-1 WD40 domain, CH3 interrupts the polymerization of And-1. Depolymerization of And-1 promotes its interaction with E3 ligase Cullin 4B (CUL4B), resulting in its ubiquitination and subsequent degradation. Furthermore, CH3 suppresses the growth of a broad range of cancers. Moreover, And-1 inhibitors re-sensitize platinum-resistant ovarian cancer cells to platinum drugs in vitro and in vivo. Since BZA is an FDA approved drug, we expect a clinical trial of BZA-mediated cancer therapy in the near future. Taken together, our findings suggest that targeting And-1 by its inhibitors is a potential broad-spectrum anti-cancer chemotherapy regimen.","journal":"Clinical and Translational Medicine","year":2021,"id":182438,"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":15,"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":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329213,"name":"Yi Zhang","orcid":"0000-0001-8170-9983","position":1,"is_corresponding":false},{"id":672398,"name":"Jing Sun","orcid":"0000-0001-6865-9862","position":2,"is_corresponding":false},{"id":734762,"name":"Leyuan Chen","orcid":"0000-0002-5508-2440","position":3,"is_corresponding":false},{"id":734763,"name":"Wenfeng Gou","orcid":"0000-0002-4828-4298","position":4,"is_corresponding":false},{"id":559421,"name":"Chi‐Wei Chen","orcid":"0000-0001-8658-055X","position":5,"is_corresponding":false},{"id":734764,"name":"Yuan Zhou","orcid":"0000-0002-4349-9476","position":6,"is_corresponding":false},{"id":672399,"name":"Zhuqing Li","orcid":"0009-0003-6568-7202","position":7,"is_corresponding":false},{"id":672405,"name":"David W. Chan","orcid":"0000-0002-6951-3467","position":8,"is_corresponding":false},{"id":408768,"name":"Ruili Huang","orcid":"0000-0002-0222-2817","position":9,"is_corresponding":false},{"id":665006,"name":"Huadong Pei","orcid":"0000-0002-5776-2060","position":10,"is_corresponding":false},{"id":227992,"name":"Wei Zheng","orcid":"0000-0003-1034-0757","position":11,"is_corresponding":false},{"id":672406,"name":"Yiliang Li","orcid":"0000-0002-3592-6167","position":12,"is_corresponding":false},{"id":355263,"name":"Menghang Xia","orcid":"0000-0001-7285-8469","position":13,"is_corresponding":false},{"id":672407,"name":"Wenge Zhu","orcid":"0000-0001-9113-5020","position":14,"is_corresponding":false},{"id":515029,"name":"Jing Li","orcid":"0000-0002-0079-693X","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"34923765","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":[]}