ArticleNAR cancer2020
The chemotherapeutic agent CX-5461 irreversibly blocks RNA polymerase I initiation and promoter release to cause nucleolar disruption, DNA damage and cell inviability.
Article in NAR cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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.
The trial behind it
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
51 citing papers in PubMed, 82 citations in OpenAlex.
- G-quadruplex DNA reprograms the photochemistry of CX-5461 toward radical-driven anticancer activity.Nucleic acids research · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Active RNA synthesis patterns nuclear condensates.Cell systems · 2026Article
- Angelicin: A promising tricyclic aromatic agent for ulcerative colitis through cysteine-mediated proliferation of intestinal epithelial cells.Journal of pharmaceutical analysis · 2026Article
- Article
- Coacervate droplets as pH-regionalized protocells.Nature communications · 2026Article
- TFEB confers resistance against the chemotherapeutic agent CX-5461.Autophagy reports · 2026Article
- Clinical significance and functional characterization of RRN3 in gastric cancer: insights from pan-cancer analysis and experimental validation.Frontiers in oncology · 2026Article
- How Early-Life Programming During Embryogenesis Imprints Cellular Memory.International journal of molecular sciences · 2025Review
- Dual RNA Polymerase I Inhibition with CX-5461 and BMH-21 Synergizes in Breast Cancer by Activating p53-Dependent Stress.bioRxiv : the preprint server for biology · 2025Article
- Article
- NPM1 mislocalization mediated by RNA Pol I inhibition alters chromatin landscape.bioRxiv : the preprint server for biology · 2025Article
- The ribosomal RNA transcription landscapes of Plasmodium falciparum and related apicomplexan parasites.Nucleic acids research · 2025Review
- In Silico Investigation of TATA-Binding Protein as a Therapeutic Target for Chagas Disease: Insights into FDA Drug Repositioning.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- APE1 condensation in nucleoli of non-cancer cells depends on rRNA transcription and forming G-quadruplex RNA structures.Nucleic acids research · 2025Article
- Ribosome biogenesis rate, a parameter of sensitivity to chemotherapeutic drugs inhibiting rRNA synthesis.Oncology reviews · 2025Review
- The Interplay Between theInternational journal of molecular sciences · 2024Review
- The unique Pt(II)-induced nucleolar stress response and its deviation from DNA damage response pathways.The Journal of biological chemistry · 2024Article
- Molecular basis of CX-5461-induced DNA damage response in primary vascular smooth muscle cells.Heliyon · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the search for drugs to effectively treat cancer, the last 10 years have seen a resurgence of interest in targeting ribosome biogenesis. CX-5461 is a potential inhibitor of ribosomal RNA synthesis that is now showing promise in phase I trials as a chemotherapeutic agent for a range of malignancies. Here, we show that CX-5461 irreversibly inhibits ribosomal RNA transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex. CX-5461 does not achieve this by preventing formation of the pre-initiation complex nor does it affect the promoter recruitment of the SL1 TBP complex or the HMGB-box upstream binding factor (UBF/UBTF). CX-5461 also does not prevent the subsequent recruitment of the initiation-competent RPI-Rrn3 complex. Rather, CX-5461 blocks promoter release of RPI-Rrn3, which remains irreversibly locked in the pre-initiation complex even after extensive drug removal. Unexpectedly, this results in an unproductive mode of RPI recruitment that correlates with the onset of nucleolar stress, inhibition of DNA replication, genome-wide DNA damage and cellular senescence. Our data demonstrate that the cytotoxicity of CX-5461 is at least in part the result of an irreversible inhibition of RPI transcription initiation and hence are of direct relevance to the design of improved strategies of chemotherapy.
Identifiers
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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.