Evidence map›Paper›PMID 40151250›Full record

ArticleJACS Au2025

Structural Basis for Inhibition of Urate Reabsorption in URAT1.

Junping Fan, Wenjun Xie, Han Ke, Jing Zhang, Jin Wang, Haijun Wang, Nianxin Guo, Yingjie Bai, Xiaoguang Lei

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACS Au, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Triple-Probiotic-Fermented Goji (Microorganisms · 2025
    Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Junping FanBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.ORCID https://orcid.org/0000-0002-2615-8098
Wenjun XieBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Han KeBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Jing ZhangJiangsu JITRI Molecular Engineering Inst. Co., Ltd., Jiangsu 215500, China.
Jin WangBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Haijun WangBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Nianxin GuoBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Yingjie BaiInstitute for Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518107, China.
Xiaoguang LeiBeijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Organic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.ORCID https://orcid.org/0000-0002-0380-8035

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The urate transporter 1 (URAT1) is the primary urate transporter in the kidney responsible for urate reabsorption and, therefore, is crucial for urate homeostasis. Hyperuricemia causes the common human disease gout and other pathological consequences. Inhibition of urate reabsorption through URAT1 has been shown as a promising strategy in alleviating hyperuricemia, and clinical and preclinical drug candidates targeting URAT1 are emerging. However, how small molecules inhibit URAT1 remains undefined, and the lack of accurate URAT1 complex structures hinders the development of better therapeutics. Here, we present cryoelectron microscopy structures of a humanized rat URAT1 bound with benzbromarone, lingdolinurad, and verinurad, elucidating the structural basis for drug recognition and inhibition. The three small molecules reside in the URAT1 central cavity with different binding modes, locking URAT1 in an inward-facing conformation. This study provides mechanistic insights into the drug modulation of URAT1 and sheds light on the rational design of potential URAT1-specific therapeutics for treating hyperuricemia.

Identifiers

PMID40151250
PMCPMC11937972

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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.