ArticleScience (New York, N.Y.)2015
Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 113 citations in OpenAlex.
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Pediatric sarcomas: challenges and opportunities.Genes & development · 2026Review
- Disrupting the CBFβ-SMMHC-RUNX1 oncogenic protein-protein interaction in inv(16) AML: from fusion biology to targeted therapy.Discover oncology · 2026Review
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- CBFβ-SMMHC-driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice.The Journal of clinical investigation · 2025Article
- Review
- Transcription factors in the development and treatment of immune disorders.Transcription · 2025Review
- Fusion Genes in Myeloid Malignancies.Cancers · 2024Review
- Differences in the mutational landscape of clonal hematopoiesis of indeterminate potential among races and between male and female patients with cancer.Experimental hematology · 2024Article
- N-MYC regulates cell survival via eIF4G1 in inv(16) acute myeloid leukemia.Science advances · 2024Article
- Histone deacetylase inhibitors: targeting epigenetic regulation in the treatment of acute leukemia.Therapeutic advances in hematology · 2024Review
- Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia-initiating CBFB::MYH11 oncofusion protein.The Journal of clinical investigation · 2023Article
- Facile Synthesis of Homodimeric Protein Ligands.Chembiochem : a European journal of chemical biology · 2023Article
- Analyses of Genes Critical to Tumor Survival Reveal Potential 'Supertargets': Focus on Transcription.Cancers · 2023Article
- Article
- End-to-end sequence-structure-function meta-learning predicts genome-wide chemical-protein interactions for dark proteins.PLoS computational biology · 2023Article
- Targeting RUNX1 as a novel treatment modality for pulmonary arterial hypertension.Cardiovascular research · 2022Article
- Review
- Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability.Nature communications · 2022Article
- NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.