Evidence mapPaperPMID 41226200Full record

ReviewMolecules (Basel, Switzerland)2025

Protein-Ligand Interactions in Cardiometabolic Drug Targets: Focus on Weight Loss and Cardioprotection.

Errikos Petsas, Despoina P Kiouri, Nikitas Georgiou, Gerasimos Siasos, Thomas Mavromoustakos, Christos T Chasapis

Erratum issuedAbstract readReview
In one paragraph

Review in Molecules (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Errikos PetsasLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 11571 Athens, Greece.ORCID 0009-0001-3805-6558
Despoina P KiouriLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 11571 Athens, Greece.ORCID 0009-0004-5104-8044
Nikitas GeorgiouLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 11571 Athens, Greece.ORCID 0000-0002-3226-7434
Gerasimos Siasos3rd Department of Cardiology, Thoracic Diseases General Hospital Sotiria, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Thomas MavromoustakosLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 11571 Athens, Greece.ORCID 0000-0001-5309-992X
Christos T ChasapisLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 11571 Athens, Greece.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cardiometabolic diseases (CVDs) are the leading cause of premature mortality and disability worldwide, arising from of cardiovascular and metabolic dysregulation. This review focuses on six critical therapeutic targets established in cardiometabolic regulation: GLP-1R, GIPR, FGFR1/β-Klotho, PCSK9, NF-κB, and the NLRP3 inflammasome. Drawing on curated structural datasets, we analyze the mechanisms of action and map key binding domain features that govern ligand efficacy and specificity. Dual GLP-1R/GIPR agonists, such as tirzepatide, demonstrate superior outcomes in glycemic control and weight reduction. Concurrently, inhibiting PCSK9, NF-κB, and NLRP3 helps to lower cholesterol and reduce harmful inflammation, offering cardioprotection. Structural analysis across these targets reveals complementary motifs (aromatic, hydrophobic, and polar residues). These insights guide the rational design of next-generation multi-target ligands (molecules capable of modulating two or more biological targets involved in related disease pathways, producing integrated therapeutic effects). Such integrated agents are promising for providing combined cardiovascular and metabolic benefits, thus reducing the risks associated with complex therapeutic drug combinations.

Indexed as

Cardiotonic AgentsCardiovascular DiseasesWeight LossAnimalsHumansLigandsProtein BindingCardiotonic AgentsLigandscardiometabolic diseasesFGFR1/β-KlothoGIP receptorGLP-1 receptormulti-target drug designNF-κB pathwayNLRP3 inflammasomePCSK9 inhibition

Identifiers

PMID41226200
PMCPMC12609854

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.