ArticlemBio2022
Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Calcineurin and mTOR inhibitors in kidney transplantation: integrative metamodeling on transplant survival and kidney function.International urology and nephrology · 2024Pooled it
- Reactive Oxygen Species-Responsive Signaling Networks and Oxidative Stress Adaptation in Critical Priority Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2026Review
- Uncovering actionable trade-offs of antifungal resistance in a yeast pathogen.Molecular systems biology · 2026Article
- Frontiers in fungal phosphatases: molecular diversity, regulatory mechanisms, analytical methodologies, ecological significance, and prospects for sustainable utilization.Frontiers in bioengineering and biotechnology · 2026Review
- Riboflavin inhibits growth and reduces virulence ofVirulence · 2025Article
- Artesunate Treats Aspergillus fumigatus Keratitis by Inhibiting Fungal Activity and Activating Autophagy Pathway to Reduce Corneal Inflammation.Investigative ophthalmology & visual science · 2025Article
- Article
- The calcineurin pathway regulates extreme thermotolerance, cell membrane and wall integrity, antifungal resistance, and virulence in Candida auris.PLoS pathogens · 2025Article
- Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Recent innovations and challenges in the treatment of fungal infections.Frontiers in cellular and infection microbiology · 2025Review
- Calcineurin activity in Fonsecaea pedrosoi: tacrolimus and cyclosporine A inhibited conidia growth, filamentation and showed synergism with itraconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Article
- Shuttle HAT for mild alkene transfer hydrofunctionalization.Nature communications · 2024Article
- Drug to genome to drug: a computational large-scale chemogenomics screening for novel drug candidates against sporotrichosis.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Calcineurin: The Achilles' heel of fungal pathogens.PLoS pathogens · 2023Article
- Cryptococcosis in Southern China: Insights from a Six-Year Retrospective Study in Eastern Guangdong.Infection and drug resistance · 2023Article
- Calcineurin Inhibitor CN585 Exhibits Off-Target Effects in the Human Fungal PathogenJournal of fungi (Basel, Switzerland) · 2022Article
- Calcineurin Inhibitors Synergize with Manogepix to Kill Diverse Human Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine phosphatase activity of calcineurin is conserved in mammals, and inhibition of this activity results in immunosuppression. FK506 (tacrolimus) is a naturally produced macrocyclic compound that inhibits calcineurin by binding to the immunophilin FKBP12. Previously, our fungal calcineurin-FK506-FKBP12 structure-based approaches identified a nonconserved region of FKBP12 that can be exploited for fungus-specific targeting. These studies led to the design of an FK506 analog, APX879, modified at the C-22 position, which was less immunosuppressive yet maintained antifungal activity. We now report high-resolution protein crystal structures of fungal FKBP12 and a human truncated calcineurin-FKBP12 bound to a natural FK506 analog, FK520 (ascomycin). Based on information from these structures and the success of APX879, we synthesized and screened a novel panel of C-22-modified compounds derived from both FK506 and FK520. One compound, JH-FK-05, demonstrates broad-spectrum antifungal activity
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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.