ArticleNature chemical biology2013
Small molecules intercept Notch signaling and the early secretory pathway.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- Towards a unified framework for the function of endoplasmic reticulum exit sites.Nature reviews. Molecular cell biology · 2025Review
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Interaction of chikungunya virus glycoproteins with macrophage factors controls virion production.The EMBO journal · 2024Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- The transmembrane domain of Frey1 harbors a transplantable inhibitory motif for intramembrane proteases.Cellular and molecular life sciences : CMLS · 2023Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.Journal of experimental & clinical cancer research : CR · 2022Article
- Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling.Cell death & disease · 2022Article
- Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease.JCI insight · 2022Article
- Regulation of reverse electron transfer at mitochondrial complex I by unconventional Notch action in cancer stem cells.Developmental cell · 2022Article
- Article
- Review
- HIST2H2BF Potentiates the Propagation of Cancer Stem CellsFrontiers in oncology · 2021Article
- Activating Transcription Factor 6 Mediates Inflammatory Signals in Intestinal Epithelial Cells Upon Endoplasmic Reticulum Stress.Gastroenterology · 2020Article
- HDAC Inhibitor LBH589 Suppresses the Proliferation but Enhances the Antileukemic Effect of Human γδT Cells.Molecular therapy oncolytics · 2020Article
- Expression of Notch-Hif-1α signaling pathway in liver regeneration of rats.The Journal of international medical research · 2020Article
- Intercepted-Knoevenagel condensation for the synthesis of unsymmetrical fused-tricyclic 4Tetrahedron · 2019Article
- Disruption of NOTCH signaling by a small molecule inhibitor of the transcription factor RBPJ.Scientific reports · 2019Article
- Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling has a pivotal role in numerous cell-fate decisions, and its aberrant activity leads to developmental disorders and cancer. To identify molecules that influence Notch signaling, we screened nearly 17,000 compounds using automated microscopy to monitor the trafficking and processing of a ligand-independent Notch-enhanced GFP (eGFP) reporter. Characterization of hits in vitro by biochemical and cellular assays and in vivo using zebrafish led to five validated compounds, four of which induced accumulation of the reporter at the plasma membrane by inhibiting γ-secretase. One compound, the dihydropyridine FLI-06, disrupted the Golgi apparatus in a manner distinct from that of brefeldin A and golgicide A. FLI-06 inhibited general secretion at a step before exit from the endoplasmic reticulum (ER), which was accompanied by a tubule-to-sheet morphological transition of the ER, rendering FLI-06 the first small molecule acting at such an early stage in secretory traffic. These data highlight the power of phenotypic screening to enable investigations of central cellular signaling pathways.
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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.