Evidence map›Paper›PMID 25047372›Full record

ArticleScientific reports2014

Developing hypothetical inhibition mechanism of novel urea transporter B inhibitor.

Min Li, Weng Ieong Tou, Hong Zhou, Fei Li, Huiwen Ren, Calvin Yu-Chian Chen, Baoxue Yang

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
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

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Urea-aromatic interactions in biology.Biophysical reviews · 2020
    Review
  8. Article
  9. Urea transport and clinical potential of urearetics.Current opinion in nephrology and hypertension · 2016
    Review
  10. 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

7 authors at 3 institutions in 2 countries.

Min LiThe State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Weng Ieong TouSchool of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan.
Hong ZhouThe State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Fei LiThe State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Huiwen RenThe State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Calvin Yu-Chian ChenSchool of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan.
Baoxue YangThe State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Peking University · CNChina Medical University · TWHubei University of Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Urea transporter B (UT-B) is a membrane channel protein that specifically transports urea. UT-B null mouse exhibited urea selective urine concentrating ability deficiency, which suggests the potential clinical applications of the UT-B inhibitors as novel diuretics. Primary high-throughput virtual screening (HTVS) of 50000 small-molecular drug-like compounds identified 2319 hit compounds. These 2319 compounds were screened by high-throughput screening using an erythrocyte osmotic lysis assay. Based on the pharmacological data, putative UT-B binding sites were identified by structure-based drug design and validated by ligand-based and QSAR model. Additionally, UT-B structural and functional characteristics under inhibitors treated and untreated conditions were simulated by molecular dynamics (MD). As the result, we identified four classes of compounds with UT-B inhibitory activity and predicted a human UT-B model, based on which computative binding sites were identified and validated. A novel potential mechanism of UT-B inhibitory activity was discovered by comparing UT-B from different species. Results suggest residue PHE198 in rat and mouse UT-B might block the inhibitor migration pathway. Inhibitory mechanisms of UT-B inhibitors and the functions of key residues in UT-B were proposed. The binding site analysis provides a structural basis for lead identification and optimization of UT-B inhibitors.

Indexed as

Amino Acid SequenceAnimalsBinding SitesDrug DesignErythrocytesHumansHydrogen BondingMembrane Transport ProteinsMiceMolecular Dynamics SimulationMolecular Sequence DataProtein BindingQuantitative Structure-Activity RelationshipRatsUrea TransportersMembrane Transport ProteinsUrea Transporters

Identifiers

PMID25047372
PMCPMC5376056
OpenAlexW2064912823

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.