ArticleAntimicrobial agents and chemotherapy2011
Discovery of a novel class of orally active antifungal beta-1,3-D-glucan synthase inhibitors.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 75 citations in OpenAlex.
- Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.Acta pharmaceutica Sinica. B · 2025Review
- Article
- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
- Innovative antifungal strategies to combat drug-resistantFrontiers in cellular and infection microbiology · 2025Review
- A Mini-Review of In Vitro Data forJournal of fungi (Basel, Switzerland) · 2024Review
- Ibrexafungerp: A narrative overview.Current research in microbial sciences · 2024Review
- Antibodies to Combat Fungal Infections: Development Strategies and Progress.Microorganisms · 2023Review
- Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents.Journal of fungi (Basel, Switzerland) · 2022Review
- Antifungal Resistance and the Role of New Therapeutic Agents.Current infectious disease reports · 2022Review
- Therapeutic Approaches for CombatingCurrent drug targets · 2022Review
- The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.Drugs · 2021Review
- Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins.International journal of molecular sciences · 2021Review
- Fungal cell wall: An underexploited target for antifungal therapies.PLoS pathogens · 2021Article
- Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor.Journal of fungi (Basel, Switzerland) · 2021Review
- Ibrexafungerp, a Novel Oral Triterpenoid Antifungal in Development: Overview of Antifungal Activity AgainstFrontiers in cellular and infection microbiology · 2021Review
- Novel Antifungal Agents and Their Activity againstJournal of fungi (Basel, Switzerland) · 2020Review
- Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside.Antimicrobial agents and chemotherapy · 2019Review
- Fungal Cell Wall: Emerging Antifungals and Drug Resistance.Frontiers in microbiology · 2019Review
- The Yin and Yang of Current Antifungal Therapeutic Strategies: How Can We Harness Our Natural Defenses?Frontiers in pharmacology · 2019Review
- Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The echinocandins are a class of semisynthetic natural products that target β-1,3-glucan synthase (GS). Their proven clinical efficacy combined with minimal safety issues has made the echinocandins an important asset in the management of fungal infection in a variety of patient populations. However, the echinocandins are delivered only parenterally. A screen for antifungal bioactivities combined with mechanism-of-action studies identified a class of piperazinyl-pyridazinones that target GS. The compounds exhibited in vitro activity comparable, and in some cases superior, to that of the echinocandins. The compounds inhibit GS in vitro, and there was a strong correlation between enzyme inhibition and in vitro antifungal activity. In addition, like the echinocandins, the compounds caused a leakage of cytoplasmic contents from yeast and produced a morphological response in molds characteristic of GS inhibitors. Spontaneous mutants of Saccharomyces cerevisiae with reduced susceptibility to the piperazinyl-pyridazinones had substitutions in FKS1. The sites of these substitutions were distinct from those conferring resistance to echinocandins; likewise, echinocandin-resistant isolates remained susceptible to the test compounds. Finally, we present efficacy and pharmacokinetic data on an example of the piperazinyl-pyridazinone compounds that demonstrated efficacy in a murine model of Candida glabrata infection.
Indexed as
Identifiers
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.