Evidence mapPaperPMID 40649923Full record

ArticleInternational journal of molecular sciences2025

Structure-Based Discovery of Orthosteric Non-Peptide GLP-1R Agonists via Integrated Virtual Screening and Molecular Dynamics.

Mansour S Alturki, Reem A Alkhodier, Mohamed S Gomaa, Dania A Hussein, Nada Tawfeeq, Abdulaziz H Al Khzem, Faheem H Pottoo, Shmoukh A Albugami, Mohammed F Aldawsari, Thankhoe A Rants'o

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In one paragraph

Article in International journal of molecular sciences, 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

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

3 citing papers in PubMed.

  1. Article
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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

10 authors.

Mansour S AlturkiDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0000-0001-7702-9379
Reem A AlkhodierDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia.ORCID 0000-0002-3946-6145
Mohamed S GomaaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0000-0003-2112-9092
Dania A HusseinDepartment of Pharmacology, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Nada TawfeeqDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0000-0002-9178-9021
Abdulaziz H Al KhzemDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0009-0004-0079-8646
Faheem H PottooDepartment of Pharmacology, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0000-0003-2577-7505
Shmoukh A AlbugamiCollege of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.ORCID 0009-0005-6095-8784
Mohammed F AldawsariDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.ORCID 0000-0003-1298-4863
Thankhoe A Rants'oDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0001-8585-0888

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The development of orally bioavailable non-peptidomimetic glucagon-like peptide-1 receptor agonists (GLP-1RAs) offers a promising therapeutic avenue for the treatment of type 2 diabetes mellitus (T2DM) and obesity. An extensive in silico approach combining structure-based drug design and ligand-based strategies together with pharmacokinetic properties and drug-likeness predictions is implemented to identify novel non-peptidic GLP-1RAs from the COCONUT and Marine Natural Products (CMNPD) libraries. More than 700,000 compounds were screened by shape-based similarity filtering in combination with precision docking against the orthosteric site of the GLP-1 receptor (PDB ID: 6X1A). The docked candidates were further assessed with the molecular mechanics MM-GBSA tool to check the binding affinities; the final list of candidates was validated by running a 500 ns long MD simulation. Twenty final hits were identified, ten from each database. The hits contained compounds with reported antidiabetic effects but with no evidence of GLP-1 agonist activity, including hits

Indexed as

Drug DiscoveryGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsMolecular Dynamics SimulationDiabetes Mellitus, Type 2HumansLigandsMolecular Docking SimulationProtein BindingGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsLigandschemical scaffoldsGLP-1Rmolecular dynamicsoral therapyvirtual screening

Identifiers

PMID40649923
PMCPMC12249819

What Socratic 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 Socratic graph.