{"doi":"10.1172/jci151109","title":"Non–beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma","abstract":"Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known SOX18 small-molecule inhibitor (Sm4) and show that this compound inhibited HemSC vessel formation in vivo with efficacy similar to that seen with the R(+) enantiomers. We next examined how R(+) propranolol alters SOX18 transcriptional activity. Using a suite of biochemical, biophysical, and quantitative molecular imaging assays, we show that R(+) propranolol directly interfered with SOX18 target gene trans-activation, disrupted SOX18-chromatin binding dynamics, and reduced SOX18 dimer formation. We propose that the R(+) enantiomers of widely used beta blockers could be repurposed to increase the efficiency of current IH treatment and lower adverse associated side effects.","journal":"Journal of Clinical Investigation","year":2021,"id":153642,"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":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"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":651560,"name":"Matthew S. Graus","orcid":"0000-0001-5470-4837","position":1,"is_corresponding":false},{"id":381506,"name":"Lan Huang","orcid":"0000-0001-9594-4722","position":2,"is_corresponding":false},{"id":651561,"name":"Alex McCann","orcid":"0000-0002-2984-5782","position":3,"is_corresponding":false},{"id":459583,"name":"Jill Wylie‐Sears","orcid":"0000-0003-3305-8578","position":4,"is_corresponding":false},{"id":651562,"name":"Frank Fontaine","orcid":"0000-0002-3133-8093","position":5,"is_corresponding":false},{"id":651563,"name":"Tara Karnezis","orcid":"0000-0003-1996-227X","position":6,"is_corresponding":false},{"id":412144,"name":"David Zurakowski","orcid":"0000-0003-3610-6942","position":7,"is_corresponding":false},{"id":651564,"name":"Steven J. Staffa","orcid":"0000-0002-7588-7596","position":8,"is_corresponding":false},{"id":302575,"name":"Frédéric A. Meunier","orcid":"0000-0001-6400-1107","position":9,"is_corresponding":false},{"id":439156,"name":"John B. Mulliken","orcid":null,"position":10,"is_corresponding":false},{"id":381507,"name":"Joyce Bischoff","orcid":"0000-0002-6367-1974","position":11,"is_corresponding":false},{"id":499669,"name":"Mathias François","orcid":"0000-0002-9846-6882","position":12,"is_corresponding":false},{"id":652536,"name":"Caroline T. Seebauer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:43:44.759273Z","pmid":"34874911","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":[]}