ArticleScientific reports2016
Mechanism of high affinity inhibition of the human urate transporter URAT1.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03425708 (Study on the Effect of Hyperuricaemia on Chronic Renal Disease and Intervention), which is not on this map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Study on the Effect of Hyperuricaemia on Chronic Renal Disease and Intervention
Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
- Molecular mechanism of drug inhibition of URAT1.Nature communications · 2025Article
- Molecular basis of the urate transporter URAT1 inhibition by gout drugs.Nature communications · 2025Article
- Article
- Mechanisms of urate transport and uricosuric drugs inhibition in human URAT1.Nature communications · 2025Article
- Investigating the Role of Food-Derived Peptides in Hyperuricemia: From Mechanisms of Action to Structural Effects.Foods (Basel, Switzerland) · 2024Review
- Transport mechanism and structural pharmacology of human urate transporter URAT1.Cell research · 2024Article
- Molecular basis of the urate transporter URAT1 inhibition by gout drugs.bioRxiv : the preprint server for biology · 2024Article
- A System for Discovering Novel Uricosurics Targeting Urate Transporter 1 Based on In Vitro and In Vivo Modeling.Pharmaceutics · 2024Article
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- Molecular basis for selective uptake and elimination of organic anions in the kidney by OAT1.Nature structural & molecular biology · 2023Article
- A State-of-the-Science Review of Interactions of Per- and Polyfluoroalkyl Substances (PFAS) with Renal Transporters in Health and Disease: Implications for Population Variability in PFAS Toxicokinetics.Environmental health perspectives · 2023Review
- Altered Serum Uric Acid Levels in Kidney Disorders.Life (Basel, Switzerland) · 2022Review
- Mutation in Transmembrane Domain 8 of Human Urate Transporter 1 Disrupts Uric Acid Recognition and Transport.ACS omega · 2022Article
- Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine.Clinical pharmacology and therapeutics · 2022Article
- EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer.iScience · 2022Article
- CDER167, a dual inhibitor of URAT1 and GLUT9, is a novel and potent uricosuric candidate for the treatment of hyperuricemia.Acta pharmacologica Sinica · 2022Article
- Urate transport in health and disease.Best practice & research. Clinical rheumatology · 2021Review
- Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release.International journal of molecular sciences · 2021Article
- The impact of an URAT1 polymorphism on the losartan treatment of hypertension and hyperuricemia.Journal of clinical laboratory analysis · 2021Article
- Renal disorders in rheumatologic diseases: the spectrum is changing (part 2. Arthridides).Journal of nephrology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. We exploited affinity differences between the human and rat transporters to map inhibitor binding sites in URAT1. Human-rat transporter chimeras revealed that human URAT1 serine-35, phenylalanine-365 and isoleucine-481 are necessary and sufficient to provide up to a 100-fold increase in affinity for inhibitors. Moreover, serine-35 and phenylalanine-365 are important for high-affinity interaction with the substrate urate. A novel URAT1 binding assay provides support for direct interaction with these amino acids; thus, current clinically important URAT1 inhibitors likely bind the same site in URAT1. A structural model suggests that these three URAT1 residues are in close proximity potentially projecting within the channel. Our results indicate that amino acids from several transmembrane segments functionally cooperate to form a high-affinity URAT1 inhibitor binding site that, when occupied, prevents substrate interactions.
Indexed as
Identifiers
What OpenQuestion holds
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.