ArticleProceedings of the National Academy of Sciences of the United States of America2012
Amphotericin primarily kills yeast by simply binding ergosterol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07215273 (A Phase 2, Multicenter, Randomized, Double-blind Study of Safety and Efficacy of EL219), which is not on this map. Cited by 288 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 2, Multicenter, Randomized, Double-blind Study of Safety and Efficacy of EL219 (Turletricin) Versus Liposomal Amphotericin B or Voriconazole for Early Antifungal Therapy of Invasive Mould Infections (TREAT-1)
Who cites it
288 citing papers in PubMed, 1 synthesis or guideline pooled it, 590 citations in OpenAlex.
- Histone deacetylase-mediated regulation of endolysosomal pH.The Journal of biological chemistry · 2018Pooled it
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- Canalesolide A, a Structurally Unique Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania sp. with Potent Antitrypanosomal Activity.Journal of the American Chemical Society · 2026Article
- Unpacking amphotericin B toxicity: a critical review of amphotericin B aggregation and its link to toxicity and antifungal activity.Archives of toxicology · 2026Review
- Lanosterol synthase inhibition as a potential approach for re-sensitizing triazole-resistantmBio · 2026Article
- Whole genome sequencing analysis of Candida glabrata isolates collected from patients with selected drug-resistant candidiasis hospitalized in Eastern Poland.Folia microbiologica · 2026Article
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- Differential Effects of Low-Intensity Pulsed Ultrasound and Antifungals onJournal of fungi (Basel, Switzerland) · 2026Article
- Ergosterol-Dependent Membrane Stress and Calcineurin-HSP90 Signaling Govern Fluorinated Sulfone-Induced Cell Death in Candida albicans.Mycopathologia · 2026Article
- Nectriatides with No Antifungal Activity Bind to Ergosterol and Potentiate the Antifungal Activity of Amphotericin B againstACS omega · 2026Article
- Chitosan-Coated Mesoporous Silica Nanoparticles Co-Loaded with Curcumin and Amphotericin B: A Drug Delivery Approach for Photodynamic Inhibition of Dual-Species Biofilms.Pharmaceutics · 2026Article
- Label-Free Visualization of the Antifungal Polyene Drug, Nystatin, in Biological Membranes Using Raman Microscopy.Analytical chemistry · 2026Article
- Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis.The Journal of cell biology · 2026Article
- Targeting the polyene chain represents an adjuvant strategy for optimizing polyene antifungals.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces.Scientific reports · 2026Article
- Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026Review
- Polypharmacology in malaria treatment: single drugs, multiple mechanisms, greater impact.Trends in parasitology · 2026Review
- Boron's Double Edge-Antibiotics, Toxins, and the Fine Line Between Them.Molecules (Basel, Switzerland) · 2026Review
228 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Amphotericin B (AmB) is a prototypical small molecule natural product that can form ion channels in living eukaryotic cells and has remained refractory to microbial resistance despite extensive clinical utilization in the treatment of life-threatening fungal infections for more than half a century. It is now widely accepted that AmB kills yeast primarily via channel-mediated membrane permeabilization. Enabled by the iterative cross-coupling-based synthesis of a functional group deficient derivative of this natural product, we have discovered that channel formation is not required for potent fungicidal activity. Alternatively, AmB primarily kills yeast by simply binding ergosterol, a lipid that is vital for many aspects of yeast cell physiology. Membrane permeabilization via channel formation represents a second complementary mechanism that further increases drug potency and the rate of yeast killing. Collectively, these findings (i) reveal that the binding of a physiologically important microbial lipid is a powerful and clinically validated antimicrobial strategy that may be inherently refractory to resistance, (ii) illuminate a more straightforward path to an improved therapeutic index for this clinically vital but also highly toxic antifungal agent, and (iii) suggest that the capacity for AmB to form protein-like ion channels might be separable from its cytocidal effects.
Indexed as
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What OpenQuestion holds
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.