ArticleNature communications2025
Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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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
6 citing papers in PubMed.
- Imidazo[1,2‑ACS omega · 2026Review
- Advancing the Understanding of the Mo-CBPProbiotics and antimicrobial proteins · 2026Article
- The pathogenicity and future treatment strategies ofFrontiers in cellular and infection microbiology · 2026Review
- Sterol-C4-methyl-oxidase Erg251 governs Candida albicans hypoxic growth, commensalism and virulence.Nature communications · 2025Article
- Structure-activity Relationship for Diarylpyrazoles as Inhibitors of the Fungal Kinase Yck2.bioRxiv : the preprint server for biology · 2025Article
- Chemoproteomic Profiling ofJournal of medicinal chemistry · 2025Article
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14 authors.
Funding
Abstract
Candida albicans is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against C. albicans revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2. Here, we report optimization of GW via two complementary approaches, synthesis of bioisosteres possessing an imidazo[1,2-a]pyridine core, and R-group substitution of GW's pyrazolo[1,5-a]pyridine core. Characterization of compounds reveals two 6-cyano derivatives with improved pharmacological properties that retain whole-cell bioactivity and selectivity for fungal Yck2 compared to human CK1α. Efficacy studies in mice indicate both analogs possess single-agent activity against C. albicans resistant to first-line echinocandin antifungals and potentiate non-curative echinocandin treatment. Results validate Yck2 as an antifungal target and encourage further development of inhibitors acting by this previously unexploited mode of action.
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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.