Integrating network pharmacology and molecular simulations to identify Doconexent-associated regulatory networks in renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is increasingly recognized as being influenced by gut microbiota-associated metabolites, although the underlying regulatory mechanisms remain unclear. In this study, an integrated network pharmacology framework was applied to systematically investigate the role of microbial metabolites in RCC. A total of 62 overlapping targets were identified and found to be significantly enriched in MAPK signaling and inflammation-related pathways. Network analysis highlighted Doconexent as a central metabolite associated with key regulatory genes. Protein–protein interaction analysis identified MAPK1 and MAPK14 as core targets. Molecular docking demonstrated favorable binding affinities between Doconexent and these proteins, which were further supported by molecular dynamics simulations indicating relatively stable protein–ligand complexes. In silico pharmacokinetic and toxicity assessments indicated that Doconexent possesses favorable drug-like properties and a satisfactory safety profile. Collectively, these findings suggest that gut microbiota-associated metabolites may contribute to RCC progression through coordinated regulation of key signaling pathways, and identify Doconexent as a potential bioactive metabolite worthy of further investigation.