ArticleJournal of the American Chemical Society2019
Ipomoeassin F Binds Sec61α to Inhibit Protein Translocation.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
51 citing papers in PubMed, 94 citations in OpenAlex.
- Cotranslational membrane protein biogenesis by an EMC-bound translocon.Nature structural & molecular biology · 2026Article
- Progress and application of activity-based protein profiling for the discovery of natural product targets.Molecular diversity · 2026Review
- Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress.Journal of natural products · 2026Article
- Buruli ulcer.Nature reviews. Disease primers · 2025Review
- Effect of Ipomoeassin F on the Synthesis of Membrane and Secretory Proteins in Triple-Negative Breast Cancer Cells.ACS omega · 2025Article
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- Lipid Scrambling Pathways in the Sec61 Translocon Complex.Journal of the American Chemical Society · 2025Article
- TheeLife · 2025Article
- Structural Modifications Reveal Dual Functions of the C-4 Carbonyl Group in the Fatty Acid Chain of Ipomoeassin F.Molecules (Basel, Switzerland) · 2025Article
- Endocytic recycling is central to circadian collagen fibrillogenesis and disrupted in fibrosis.eLife · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 2025Review
- Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis inbioRxiv : the preprint server for biology · 2024Article
- A unifying model for membrane protein biogenesis.Nature structural & molecular biology · 2024Review
- Article
- Diastereomers of Coibamide A Show Altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-Derived Glioma Stem-like Cells.ACS pharmacology & translational science · 2024Article
- Design of Synthetic Surrogates for the Macrolactone Linker Motif in Coibamide A.ACS medicinal chemistry letters · 2023Article
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
- Leader peptide or pro-segment mutants of renin are misrouted to mitochondria in autosomal dominant tubulointerstitial kidney disease.Disease models & mechanisms · 2023Article
- Review
Corrections and comments
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Authors and funding
23 authors at 11 institutions in 4 countries.
Funding
Abstract
Ipomoeassin F is a potent natural cytotoxin that inhibits growth of many tumor cell lines with single-digit nanomolar potency. However, its biological and pharmacological properties have remained largely unexplored. Building upon our earlier achievements in total synthesis and medicinal chemistry, we used chemical proteomics to identify Sec61α (protein transport protein Sec61 subunit alpha isoform 1), the pore-forming subunit of the Sec61 protein translocon, as a direct binding partner of ipomoeassin F in living cells. The interaction is specific and strong enough to survive lysis conditions, enabling a biotin analogue of ipomoeassin F to pull down Sec61α from live cells, yet it is also reversible, as judged by several experiments including fluorescent streptavidin staining, delayed competition in affinity pulldown, and inhibition of TNF biogenesis after washout. Sec61α forms the central subunit of the ER protein translocation complex, and the binding of ipomoeassin F results in a substantial, yet selective, inhibition of protein translocation in vitro and a broad ranging inhibition of protein secretion in live cells. Lastly, the unique resistance profile demonstrated by specific amino acid single-point mutations in Sec61α provides compelling evidence that Sec61α is the primary molecular target of ipomoeassin F and strongly suggests that the binding of this natural product to Sec61α is distinctive. Therefore, ipomoeassin F represents the first plant-derived, carbohydrate-based member of a novel structural class that offers new opportunities to explore Sec61α function and to further investigate its potential as a therapeutic target for drug discovery.
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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.