ArticleNature communications2025
Molecular mechanism of drug inhibition of URAT1.
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 3 papers.
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Who cites it
3 citing papers in PubMed.
- ABCG2 transporter: Structural and functional associations with gout (Review).International journal of molecular medicine · 2026Review
- Hirudin Attenuates Uric Acid-Induced Renal Tubular Injury via TNFRSF6B-Mediated Suppression of NF-κB Signaling.Pharmacology research & perspectives · 2026Article
- Urate transporters: Structural mechanisms and therapeutic opportunities in drug development.Acta pharmaceutica Sinica. B · 2026Article
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Authors and funding
13 authors.
Funding
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Abstract
Hyperuricemia, characterized by elevated serum urate levels, is a key factor in the pathogenesis of gout. URAT1 is essential for renal urate reabsorption and has emerged as a critical therapeutic target for managing hyperuricemia. However, the precise transport mechanism and the inhibitory effects of uricosuric drugs on URAT1 remain unclear. Here, we present structures of the double-mutant rat homolog of URAT1 in complex with its substrate urate, and the clinical drugs benzbromarone, lesinurad, verinurad, and sulfinpyrazone. The urate-bound structure elucidates key residues involved in recognizing urate, while the structures bound with drugs clearly demonstrate the distinct binding mode of each drug with URAT1. These drugs stabilize URAT1's inward-facing state, blocking conformational transitions. Additionally, critical interactions essential for its conformational transition are identified. These findings provide a molecular framework for understanding the physiological function of URAT1 and for developing more efficacious therapies to treat hyperuricemia.
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