ArticleScientific reports2018
The Notch inhibitor cowanin accelerates nicastrin degradation.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.The Journal of antibiotics · 2024Article
- Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.Frontiers in pharmacology · 2024Review
- Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids.Investigative ophthalmology & visual science · 2022Article
- Identification of 1β,2α-epoxytagitinin C as a Notch inhibitor, oxidative stress mechanism and its anti-leukemia activity.Journal of natural medicines · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Isolation of nocobactin NAs as Notch signal inhibitors from Nocardia farcinica, a possibility of invasive evolution.The Journal of antibiotics · 2021Article
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- Article
- Review
- Isolation and evaluation of cardenolides from Lansium domesticum as Notch inhibitors.Journal of natural medicines · 2020Article
- The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway.Oxidative medicine and cellular longevity · 2019Review
- Oleandrin and Its Derivative Odoroside A, Both Cardiac Glycosides, Exhibit Anticancer Effects by Inhibiting Invasion via Suppressing the STAT-3 Signaling Pathway.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of Notch signaling contributes to the pathogenesis of several different types of cancer, and Notch pathway inhibitors may have significant therapeutic potential. Using a unique cell-based assay system, we isolated twelve compounds, including one new natural product from Garcinia speciosa, that inhibit the Notch signaling pathway. HES1 and HES5 are target genes of the Notch cascade, and compound 2, referred to as cowanin, decreased the protein levels of HES1 and HES5 in assay cells. Furthermore, cowanin (2) showed potent cytotoxicity against human leukemic HPB-ALL cells. The Notch signaling inhibitory activity of cowanin (2) is linked to the increased degradation of nicastrin, which is one of the components of the γ-secretase complex. To the best of our knowledge, this is the first example of a compound with Notch pathway inhibitory activity mediated by nicastrin degradation.
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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.