{"doi":"10.3390/cancers14225544","title":"RNA Polymerase I Is Uniquely Vulnerable to the Small-Molecule Inhibitor BMH-21","abstract":"Cancer cells require robust ribosome biogenesis to maintain rapid cell growth during tumorigenesis. Because RNA polymerase I (Pol I) transcription of the ribosomal DNA (rDNA) is the first and rate-limiting step of ribosome biogenesis, it has emerged as a promising anti-cancer target. Over the last decade, novel cancer therapeutics targeting Pol I have progressed to clinical trials. BMH-21 is a first-in-class small molecule that inhibits Pol I transcription and represses cancer cell growth. Several recent studies have uncovered key mechanisms by which BMH-21 inhibits ribosome biosynthesis but the selectivity of BMH-21 for Pol I has not been directly measured. Here, we quantify the effects of BMH-21 on Pol I, RNA polymerase II (Pol II), and RNA polymerase III (Pol III) in vitro using purified components. We found that BMH-21 directly impairs nucleotide addition by Pol I, with no or modest effect on Pols II and III, respectively. Additionally, we found that BMH-21 does not affect the stability of any of the Pols' elongation complexes. These data demonstrate that BMH-21 directly exploits unique vulnerabilities of Pol I.","journal":"Cancers","year":2022,"id":251486,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":894822,"name":"Kaila B. Fuller","orcid":"0000-0001-9570-389X","position":1,"is_corresponding":false},{"id":895454,"name":"Stephanie Cooper","orcid":null,"position":2,"is_corresponding":false},{"id":894823,"name":"Zachariah I. Carter","orcid":"0000-0001-5717-7331","position":3,"is_corresponding":false},{"id":649815,"name":"Marikki Laiho","orcid":"0000-0002-5625-6430","position":4,"is_corresponding":false},{"id":504475,"name":"Aaron L. Lucius","orcid":"0000-0001-8636-5411","position":5,"is_corresponding":false},{"id":504476,"name":"David A. Schneider","orcid":"0000-0003-0635-5091","position":6,"is_corresponding":false},{"id":504474,"name":"Ruth Q. Jacobs","orcid":"0000-0002-7854-7941","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T00:24:41.993282Z","pmid":"36428638","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":[]}