Evidence map›Paper›PMID 40842311›Full record

ArticleChemistryOpen2025

Structure-Guided Identification and Evaluation of Epalrestat and Ranirestat-Like Compounds Against Aldose Reductase: Therapeutic Management of Diabetic Neuropathy.

Mohd Shahnawaz Khan, Dharmendra Kumar Yadav, Moyad Shahwan, Anas Shamsi

Abstract read
In one paragraph

Article in ChemistryOpen, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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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

3 citing papers in PubMed.

  1. Article
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  3. Review
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

4 authors.

Mohd Shahnawaz KhanDepartment of Biochemistry, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Dharmendra Kumar YadavGachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, Incheon, 21936, Republic of Korea.ORCID 0000-0003-1102-1993
Moyad ShahwanDepartment of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, UAE.
Anas ShamsiCentre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, 346, UAE.ORCID 0000-0001-7055-7056

Funding

Ajman UniversityKing Saud University, Ongoing Research Funding Program ORF-2025-352
6 · The paper itself

Abstract

Aldose reductase (ALDR) is a critical protein involved in the pathogenesis of diabetic complications such as retinopathy, neuropathy, and nephropathy. Due to the activation of inflammatory and cytotoxic pathways under hyperglycemic conditions, ALDR has become an important target for therapeutic development. Currently, available drugs such as epalrestat and ranirestat are suboptimal due to factors such as toxicity and low solubility. In this study, a structure-based approach was used to screen the PubChem database to identify novel ALDR inhibitors with a Tanimoto coefficient greater than 0.8 with the structural frameworks of epalrestat and ranirestat. A systematic virtual screening, including molecular docking, drug-likeness assessment, and molecular dynamics (MD) simulations, revealed two promising candidates, PubChem CIDs: 45110135 and 58643777. These compounds showed higher binding and selectivity toward ALDR than epalrestat and ranirestat in docking studies. MD simulations supported the stability and preferred dynamics of their interactions with ALDR. These findings suggest that compounds CID:45110135 (N-[3-fluoro-4-(4-fluoro-1,3-dioxoisoindol-2-yl)phenyl]pyridine-2-carboxamide) and CID:58643777 ([(5Z)-4-oxo-2-sulfanylidene-5-[[3-[3-(trifluoromethyl)phenyl]phenyl]methylidene]-1,3-thiazolidin-3-yl]propanoic acid) might have the potential to be lead compounds for the development of new drugs for diabetic neuropathy after required validation.

Indexed as

Aldehyde ReductaseDiabetic NeuropathiesEnzyme InhibitorsRhodanineSpiro CompoundsThiazolidinesHumansMolecular Docking SimulationMolecular Dynamics SimulationMolecular StructurePyrazinesStructure-Activity RelationshipAldehyde ReductaseEnzyme InhibitorsepalrestatPyrazinesranirestatRhodanineSpiro CompoundsThiazolidinesaldose reductase inhibitorsbinding affinitydiabetic neuropathymolecular dynamics simulationsvirtual screening

Identifiers

PMID40842311
PMCPMC12680551

What OpenQuestion holds

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Registered trials

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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.