ArticleCancer research2021
Pharmacological Disruption of the Notch1 Transcriptional Complex Inhibits Tumor Growth by Selectively Targeting Cancer Stem Cells.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 26 citations in OpenAlex.
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- SIDISH integrates single-cell and bulk transcriptomics to identify high-risk cells and guide precision therapeutics through in silico perturbation.Nature communications · 2025Article
- Emerging nanoparticles that target and eliminate cancer stem cells.Nanomedicine (London, England) · 2025Review
- Single-cell multi-omics and machine learning for dissecting stemness in cancer.Briefings in bioinformatics · 2025Review
- γ-Glutamylcyclotransferase is transcriptionally regulated by c-Jun and controls proliferation of glioblastoma stem cells through Notch1 levels.Cancer gene therapy · 2024Article
- Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- ASPM stabilizes the NOTCH intracellular domain 1 and promotes oncogenesis by blocking FBXW7 binding in hepatocellular carcinoma cells.Molecular oncology · 2024Article
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- New tricks for an old pathway: emerging Notch-based biotechnologies and therapeutics.Trends in pharmacological sciences · 2023Review
- Notch signaling regulates a metabolic switch through inhibiting PGC-1α and mitochondrial biogenesis in dedifferentiated liposarcoma.Oncogene · 2023Article
- A novel chemical attack on Notch-mediated transcription by targeting the NACK ATPase.Molecular therapy oncolytics · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Article
- Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma.Cells · 2022Review
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- Notch signalling in healthy and diseased vasculature.Open biology · 2022Review
- Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche.Frontiers in immunology · 2022Review
- Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
In many human cancers, deregulation of the Notch pathway has been shown to play a role in the initiation and maintenance of the neoplastic phenotype. Aberrant Notch activity also plays a central role in the maintenance and survival of cancer stem cells (CSC), which underlie metastasis and resistance to therapy. For these reasons, inhibition of Notch signaling has become an exceedingly attractive target for cancer therapeutic development. However, attempts to develop Notch pathway-specific drugs have largely failed in the clinic, in part due to intestinal toxicity. Here, we report the discovery of NADI-351, the first specific small-molecule inhibitor of Notch1 transcriptional complexes. NADI-351 selectively disrupted Notch1 transcription complexes and reduced Notch1 recruitment to target genes. NADI-351 demonstrated robust antitumor activity without inducing intestinal toxicity in mouse models, and CSCs were ablated by NADI-351 treatment. Our study demonstrates that NADI-351 is an orally available and potent inhibitor of Notch1-mediated transcription that inhibits tumor growth with low toxicity, providing a potential therapeutic approach for improved cancer treatment. SIGNIFICANCE: This study showcases the first Notch1-selective inhibitor that suppresses tumor growth with limited toxicity by selectively ablating cancer stem cells.
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What Socratic holds
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 Socratic graph.