ArticleProceedings of the National Academy of Sciences of the United States of America2020
Pharmacological disruption of the Notch transcription factor complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- Targeting mannosylation of nicastrin N-glycans attenuates γ-secretase activity and notch-dependent leukemia progression.The Journal of clinical investigation · 2026Article
- A noncanonical role for Jagged1 in endothelial mechanotransduction.The FEBS journal · 2026Article
- Aryl hydrocarbon receptor deficiency triggers the activation of γδT17 cells to exacerbate autoimmune inflammation.Science advances · 2026Article
- Small molecule-mediated activation of Notch signal transduction.Cell death & disease · 2026Article
- Lenalidomide boosts CD1d-Vδ2 bispecific antibody-engaged Vγ9Vδ2-T cell effector functions via CD28, Notch signaling and IL-2 release.Journal for immunotherapy of cancer · 2026Article
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- Article
- Decoding NOTCH1: From T-Cell Development Guardian to Driver of Pediatric T-Cell Lymphoblastic Lymphoma.International journal of molecular sciences · 2026Review
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Intestinal epithelial cells in health and disease.Tissue barriers · 2026Review
- Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy.Blood · 2025Article
- Auranofin Synergizes with Cisplatin in Reducing Tumor Burden of NOTCH-Dependent Ovarian Cancer.Cancer research communications · 2025Article
- Transcriptional Control of TSPAN32 in T-ALL Reveals Interplay Between TAL1 and NOTCH1.Biomedicines · 2025Article
- Notch2 Deletion Compromises Epithelial Integrity and Enamel Formation in Rodent Incisors.Cells · 2025Article
- Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer.Future medicinal chemistry · 2025Review
- Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.Nature cancer · 2025Article
- Induction of T-Cell Differentiation by KLF4 in T-Cell Acute Lymphoblastic Leukemia Cells Harboring Activating Mutation in NOTCH3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Therapeutic targeting of the NOTCH1 and neddylation pathways in T cell acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Clinical Outcomes With Notch Inhibitors in Notch-Activated Recurrent/Metastatic Adenoid Cystic Carcinoma.Cancer medicine · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors.
Funding
Abstract
Notch pathway signaling is implicated in several human cancers. Aberrant activation and mutations of Notch signaling components are linked to tumor initiation, maintenance, and resistance to cancer therapy. Several strategies, such as monoclonal antibodies against Notch ligands and receptors, as well as small-molecule γ-secretase inhibitors (GSIs), have been developed to interfere with Notch receptor activation at proximal points in the pathway. However, the use of drug-like small molecules to target the downstream mediators of Notch signaling, the Notch transcription activation complex, remains largely unexplored. Here, we report the discovery of an orally active small-molecule inhibitor (termed CB-103) of the Notch transcription activation complex. We show that CB-103 inhibits Notch signaling in primary human T cell acute lymphoblastic leukemia and other Notch-dependent human tumor cell lines, and concomitantly induces cell cycle arrest and apoptosis, thereby impairing proliferation, including in GSI-resistant human tumor cell lines with chromosomal translocations and rearrangements in Notch genes. CB-103 produces Notch loss-of-function phenotypes in flies and mice and inhibits the growth of human breast cancer and leukemia xenografts, notably without causing the dose-limiting intestinal toxicity associated with other Notch inhibitors. Thus, we describe a pharmacological strategy that interferes with Notch signaling by disrupting the Notch transcription complex and shows therapeutic potential for treating Notch-driven cancers.
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