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Targeting the Crosstalk Between Metabolism and Chronic Inflammation: In Silico Multitargeting Drug Design Approach
Errikos Petsas1, Gerasimos Siasos2, Thomas Mavromoustakos1
1Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Biomedicines
|June 26, 2026
Summary
Researchers identified D4Z, a promising small molecule targeting multiple pathways involved in cardiometabolic disorders and inflammation. This computational study prioritizes D4Z for further experimental validation.
Area of Science:
- Computational chemistry
- Drug discovery
- Pharmacology
Background:
- Cardiometabolic disorders and chronic low-grade inflammation represent a significant global health challenge.
- Effective therapies require modulation of multiple interconnected biological pathways.
Purpose of the Study:
- To identify and prioritize small-molecule multitarget drug candidates.
- To computationally screen for compounds targeting PCSK9, GLP1R, FGFR1, GIPR, NF-κB, and NLRP3.
Main Methods:
- Ligand-based virtual screening using a known scaffold.
- Molecular docking and 200 ns molecular dynamics simulations.
- ADMET prediction for pharmacokinetic and physicochemical properties.
Main Results:
- D4Z was identified as a balanced lead candidate.
- D4Z demonstrated favorable binding profiles and stable interactions.
- D4Z exhibited a drug-like profile with high predicted oral absorption.
Conclusions:
- D4Z is a computationally prioritized multitarget lead for experimental validation.
- Rational multitarget drug design shows potential for addressing the cardiometabolic-inflammatory axis.
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