ArticleCell chemical biology2024
Anticancer benzoxaboroles block pre-mRNA processing by directly inhibiting CPSF3.
Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Boron-Based Bioisosteres in Medicinal Chemistry: Advances in Heterocycles and Therapeutic.ChemMedChem · 2026Review
- Molecular modeling of 7-propanamide benzoxaboroles as CPSF3 inhibitors through docking-based 3D-QSAR and molecular dynamics simulations.RSC advances · 2026Article
- Transcriptional readthrough progresses from incidental byproduct to therapeutic opportunity.Nature structural & molecular biology · 2026Article
- The competition between splicing and 3' processing shapes the human transcriptome.Genes & development · 2026Article
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- Acoziborole resistance associated mutations in Trypanosoma brucei CPSF3.PLoS pathogens · 2026Article
- Discovery of New 7-Propanamide Benzoxaborole as Potent Anti-SKOV3 Agent via 3D-QSAR Models.International journal of molecular sciences · 2026Article
- Boron-containing anticancer agents: a target-centric review of structure-activity relationships and clinical pipeline.Archives of pharmacal research · 2025Review
- Loss of CFIm activates YAP/TAZ and connects mRNA cleavage and polyadenylation inhibition to BRCAness.bioRxiv : the preprint server for biology · 2025Article
- Phenylboronic acid in targeted cancer therapy and diagnosis.Theranostics · 2025Review
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
A novel class of benzoxaboroles was reported to induce cancer cell death but the mechanism was unknown. Using a forward genetics platform, we discovered mutations in cleavage and polyadenylation specific factor 3 (CPSF3) that reduce benzoxaborole binding and confer resistance. CPSF3 is the endonuclease responsible for pre-mRNA 3'-end processing, which is also important for RNA polymerase II transcription termination. Benzoxaboroles inhibit this endonuclease activity of CPSF3 in vitro and also curb transcriptional termination in cells, which results in the downregulation of numerous constitutively expressed genes. Furthermore, we used X-ray crystallography to demonstrate that benzoxaboroles bind to the active site of CPSF3 in a manner distinct from the other known inhibitors of CPSF3. The benzoxaborole compound impeded the growth of cancer cell lines derived from different lineages. Our results suggest benzoxaboroles may represent a promising lead as CPSF3 inhibitors for clinical development.
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Registered trials
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.