ArticleEukaryotic cell2004
Discovery of cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high-throughput screening.
Article in Eukaryotic cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 111 citations in OpenAlex.
- Article
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- Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer.ACS pharmacology & translational science · 2025Review
- Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.Nature communications · 2025Article
- Chemoproteomic Profiling ofbioRxiv : the preprint server for biology · 2025Article
- Structure-guided optimization of small molecules targeting the yeast casein kinase, Yck2, as a therapeutic strategy to combat Candida albicans.Research square · 2025Article
- An evolutionarily conserved phosphoserine-arginine salt bridge in the interface between ribosomal proteins uS4 and uS5 regulates translational accuracy in Saccharomyces cerevisiae.Nucleic acids research · 2024Article
- Advancements and challenges in antifungal therapeutic development.Clinical microbiology reviews · 2024Review
- Antifungal activity of cercosporamide produced by Phaeosphaeriaceae GV-1 against pathogenic fungi.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Cercosporamide, a polyketide-derived fungal metabolite, serves as an antifungal agent against phytopathogenic fungi.Mycoscience · 2024Article
- An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.Molecular therapy. Nucleic acids · 2022Article
- Whole Genome Sequencing Analysis of Effects of CRISPR/Cas9 inJournal of fungi (Basel, Switzerland) · 2022Article
- Functional analysis of theiScience · 2022Article
- Control of Gene Expression via the Yeast CWI Pathway.International journal of molecular sciences · 2022Review
- Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases.Molecules (Basel, Switzerland) · 2021Article
- The Future of Antifungal Drug Therapy: Novel Compounds and Targets.Antimicrobial agents and chemotherapy · 2021Review
- A Highly Selective MNK Inhibitor Rescues Deficits Associated with Fragile X Syndrome in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain.Pharmacological reviews · 2021Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Pkc1-mediated cell wall integrity-signaling pathway is highly conserved in fungi and is essential for fungal growth. We thus explored the potential of targeting the Pkc1 protein kinase for developing broad-spectrum fungicidal antifungal drugs through a Candida albicans Pkc1-based high-throughput screening. We discovered that cercosporamide, a broad-spectrum natural antifungal compound, but previously with an unknown mode of action, is actually a selective and highly potent fungal Pkc1 kinase inhibitor. This finding provides a molecular explanation for previous observations in which Saccharomyces cerevisiae cell wall mutants were found to be highly sensitive to cercosporamide. Indeed, S. cerevisiae mutant cells with reduced Pkc1 kinase activity become hypersensitive to cercosporamide, and this sensitivity can be suppressed under high-osmotic growth conditions. Together, the results demonstrate that cercosporamide acts selectively on Pkc1 kinase and, thus, they provide a molecular mechanism for its antifungal activity. Furthermore, cercosporamide and a beta-1,3-glucan synthase inhibitor echinocandin analog, by targeting two different key components of the cell wall biosynthesis pathway, are highly synergistic in their antifungal activities. The synergistic antifungal activity between Pkc1 kinase and beta-1,3-glucan synthase inhibitors points to a potential highly effective combination therapy to treat fungal infections.
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