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2000
Volume 21, Issue 18
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Diabetic Nephropathy (DN) is the leading cause of the end-stage renal disease (ESRD). Finerenone (with the molecular formula CHNO) is an oral non-steroidal mineralocorticoid antagonist (ns-MRA) that is both highly potent and has strong selectivity for the MR. At present, it has been used to treat DN. However, the molecular mechanism of finerenone in the treatment of diabetic nephropathy remains unclear.

Objective

In this study, we employed bioinformatics approaches to investigate the molecular mechanism of finerenone as a novel therapeutic agent for the treatment of DN.

Methods

We examined a number of databases, including GEO, DisGeNET, Genecards, and OMIM, to find putative genes linked to DN. We then employed the PubChem database and PharmMapper service platform to identify targets of finerenone. Further analysis was conducted using the DAVID database for enrichment analysis and the STRING database for protein-protein interaction (PPI) networks. Molecular docking (MD) was performed using AutoDockTools software, and results were visualized using PyMOL software.

Results

In total, we identified 82 drug-disease targets, primarily associated with lipid and atherosclerosis, diabetic cardiomyopathy, MAPK signaling pathway, and PI3K-Akt signaling pathway. Our PPI network analysis and docking studies demonstrated good binding ability of finerenone to specific targets such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.

Conclusion

Finerenone has the potential to reduce the progression of DN through various pathways, including lipid and atherosclerosis, diabetic cardiomyopathy, MAPK signaling pathway, and PI3K-Akt signaling pathway. Moreover, it could exert anti-inflammatory and antifibrotic effects on specific targets, such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.

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Molecular Mechanism of Finerenone in Treating Diabetic Nephropathy Based on Bioinformatics
Letters in Drug Design & Discovery 21, 4389 (2024); https://doi.org/10.2174/0115701808354285241109140805
/content/journals/lddd/10.2174/0115701808354285241109140805
/content/journals/lddd/10.2174/0115701808354285241109140805
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  • Article Type:     Research Article
Keyword(s): bioinformatics; diabetic nephropathy; enrichment analysis; Finerenone; molecular docking; molecular mechanism of action

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