ArticleInternational journal of cancer2018
Bepridil exhibits anti-leukemic activity associated with NOTCH1 pathway inhibition in chronic lymphocytic leukemia.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Bcor loss promotes Richter transformation of chronic lymphocytic leukemia associated with Notch1 activation in mice.Leukemia · 2025Article
- Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways.NPJ precision oncology · 2025Article
- The role of notch signaling pathway in cancer: mechanistic insights, therapeutic potential, and clinical progress.Frontiers in immunology · 2025Review
- Nanotechnology Advances in the Detection and Treatment of Lymphoid Malignancies.International journal of molecular sciences · 2024Review
- CAD204520 TargetsInternational journal of molecular sciences · 2024Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Suppression of Metastatic Ovarian Cancer Cells by Bepridil, a Calcium Channel Blocker.Life (Basel, Switzerland) · 2023Article
- Article
- Hes1 Controls Proliferation and Apoptosis in Chronic Lymphoblastic Leukemia Cells by Modulating PTEN Expression.Molecular biotechnology · 2022Article
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- NOTCH1 inhibition prevents GvHD and maintains GvL effect in murine models.Bone marrow transplantation · 2021Article
- Bepridil, a class IV antiarrhythmic agent, can block the TREK-1 potassium channel.Annals of translational medicine · 2021Article
- The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.World journal of surgical oncology · 2021Article
- Targeting oncogenic Notch signaling with SERCA inhibitors.Journal of hematology & oncology · 2021Review
- NOTCH1 Activation Negatively Impacts on Chronic Lymphocytic Leukemia Outcome and Is Not Correlated to theFrontiers in oncology · 2021Article
- Review
- Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia.Cell chemical biology · 2020Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated NOTCH1 signaling, by either gene mutations or microenvironment interactions, has been increasingly linked to chronic lymphocytic leukemia (CLL). Thus, inhibiting NOTCH1 activity represents a potential therapeutic opportunity for this disease. Using gene expression-based screening, we identified the calcium channel modulator bepridil as a new NOTCH1 pathway inhibitor. In primary CLL cells, bepridil induced selective apoptosis even in the presence of the protective stroma. Cytotoxic effects of bepridil were independent of NOTCH1 mutation and other prognostic markers. The antitumor efficacy of bepridil was associated with inhibition of NOTCH1 activity through a decrement in trans-membrane and activated NOTCH1 protein levels with unchanged NOTCH2 protein levels. In a CLL xenotransplant model, bepridil significantly reduced the percentage of leukemic cells infiltrating the spleen via enhanced apoptosis and decreased NOTCH1 activation. In conclusion, we report in vitro and in vivo anti-leukemic activity of bepridil associated with inhibition of the NOTCH1 pathway in CLL. These data provide a rationale for the clinical development of bepridil as anti-NOTCH1 targeted therapy for CLL patients.
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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.