{"doi":"10.1016/j.stem.2023.01.008","title":"Reversal of malignant ADAR1 splice isoform switching with Rebecsinib","abstract":"Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 and splicing reporters for non-invasive detection of splicing-mediated ADAR1 adenosine-to-inosine (A-to-I) RNA editing activation; a quantitative ADAR1p150 intracellular flow cytometric assay; a selective small-molecule inhibitor of splicing-mediated ADAR1 activation, Rebecsinib, which inhibits leukemia stem cell (LSC) self-renewal and prolongs humanized LSC mouse model survival at doses that spare normal hematopoietic stem and progenitor cells (HSPCs); and pre-IND studies showing favorable Rebecsinib toxicokinetic and pharmacodynamic (TK/PD) properties. Together, these results lay the foundation for developing Rebecsinib as a clinical ADAR1p150 antagonist aimed at obviating malignant microenvironment-driven LSC generation.","journal":"Cell stem cell","year":2023,"id":318035,"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":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":666849,"name":"Wenxue Ma","orcid":"0000-0001-9228-6162","position":1,"is_corresponding":false},{"id":643448,"name":"Luisa Ladel","orcid":null,"position":2,"is_corresponding":false},{"id":666848,"name":"Jessica Pham","orcid":"0000-0002-4837-6379","position":3,"is_corresponding":false},{"id":1025029,"name":"Larisa Balaian","orcid":null,"position":4,"is_corresponding":false},{"id":1024556,"name":"Kathleen Steel","orcid":"0000-0002-4102-9577","position":5,"is_corresponding":false},{"id":653060,"name":"Phoebe Mondala","orcid":"0000-0002-2758-1701","position":6,"is_corresponding":false},{"id":666851,"name":"Raymond Diep","orcid":"0000-0003-4982-1283","position":7,"is_corresponding":false},{"id":1024557,"name":"Christina Wu","orcid":"0000-0002-5279-9032","position":8,"is_corresponding":false},{"id":666846,"name":"Cayla Mason","orcid":"0000-0003-4598-3824","position":9,"is_corresponding":false},{"id":1024558,"name":"Inge van der Werf","orcid":"0000-0002-8159-399X","position":10,"is_corresponding":false},{"id":667408,"name":"Isabelle Oliver","orcid":null,"position":11,"is_corresponding":false},{"id":667409,"name":"Eduardo Reynoso","orcid":null,"position":12,"is_corresponding":false},{"id":478300,"name":"Gabriel Pineda","orcid":null,"position":13,"is_corresponding":false},{"id":85810,"name":"Thomas Whisenant","orcid":"0000-0002-2838-1605","position":14,"is_corresponding":false},{"id":1025030,"name":"Peggy Wentworth","orcid":null,"position":15,"is_corresponding":false},{"id":295590,"name":"James J. La Clair","orcid":"0000-0001-6500-4107","position":16,"is_corresponding":false},{"id":103666,"name":"Sara Brin Rosenthal","orcid":"0000-0002-9072-8032","position":17,"is_corresponding":false},{"id":295592,"name":"Michael D. Burkart","orcid":"0000-0002-4472-2254","position":18,"is_corresponding":false},{"id":477605,"name":"Catriona Jamieson","orcid":"0000-0001-8057-6613","position":19,"is_corresponding":false},{"id":653061,"name":"Leslie Crews","orcid":"0000-0003-0704-0067","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:06:55.884740Z","pmid":"36803553","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":[]}