ArticleNature communications2025
Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization.
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.
What it found
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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.
- Urate transporters: Structural mechanisms and therapeutic opportunities in drug development.Acta pharmaceutica Sinica. B · 2026Article
- Metabolic and inflammatory mechanisms in uric acid-induced tubular dysfunction: Emerging perspectives.Clinics (Sao Paulo, Brazil) · 2026Article
- A novel dual-action drug TJ94 facilitated by lipid nanocrystal formulations targeting neuroprotection and antithrombosis in ischemic stroke.Materials today. Bio · 2026Article
- Biodiversity-Driven Natural Products and Bioactive Metabolites.Plants (Basel, Switzerland) · 2025Review
- Glycyrrhiza polysaccharide-adjuvanted liposomal vaccine potentiates tumor immunotherapy through lymph node-targeted modulation of the DC-T cell axis.Journal of experimental & clinical cancer research : CR · 2025Article
- Macropinocytosis fuels osteoclast differentiation in bone-related diseases.Journal of orthopaedic translation · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Developing anti-gout medications that simultaneously reduce uric acid and exert anti-inflammatory effects represents a critical breakthrough for managing gout progression. Natural products with polypharmacological properties offer promising leads for drug discovery. In this study, β-carboline-1-propionic acid, a bioactive constituent of Eurycoma longifolia Jack, served as the starting point for drug design. Guided by a dual-target pharmacophore model, we design and synthesize 64 derivatives. Through systematic screening, 32 emerges as a drug candidate, demonstrating potent uric acid-lowering activity in male hyperuricemia mouse models (efficacy comparable to febuxostat and superior to lesinurad and benzbromarone) by inhibiting key urate transporters. In a male rat model of acute gouty arthritis, 32 mitigates NOD-like receptor protein 3 inflammasome-mediated inflammation. Notably, 32 exhibits enhanced safety compared to control drugs. This study exemplifies a natural product-inspired, dual-mechanism drug discovery approach, showcasing the potential of a rational polypharmacology and thus offering therapeutic opportunities for gout management.
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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 Socratic graph.