Identification of Natural Compounds as Potential FGFR2 Inhibitors in Cholangiocarcinoma via Virtual Screening and Network-Based Analysis
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https://doi.org/10.62482/pmj.28Keywords:
FGFR2, cholangiocarcinoma, molecular docking, natural compounds, ADMET analysisAbstract
Introduction: Cholangiocarcinoma is an aggressive neoplasm of bile duct epithelial cells with poor prognosis due to limited treatment options. Fibroblast growth factor receptor 2 (FGFR2) is critical in cholangiocarcinoma by activating pathways such as MAPK/ERK and PI3K/AKT, marking it as a promising therapeutic target. This study aimed to identify natural FGFR2 inhibitors by using computational methods.
Methods: 46 natural compounds were selected from PubChem based on favorable physicochemical properties and drug-likeness criteria. Molecular docking was performed using SwissDock against FGFR2 (PDB ID: 4J97). The top five compounds were further assessed for pharmacokinetics, pharmacodynamics, and toxicity via SwissADME, pkCSM, and DeepPK tools. Additionally, protein-protein interaction networks and pathway enrichment analyses were conducted using the STRING database and KEGG.
Results: Docking analysis identified Rutecarpine, Palonosetron, Metribolone, 6-Ketoestradiol, and Gestrinone as the top FGFR2 inhibitors, with docking scores between – 6.34 and – 5.95 kcal/mol. ADMET predictions showed favorable drug- like properties, good bioavailability, and acceptable safety profiles. Network and pathway analyses confirmed FGFR2’s role in key oncogenic pathways, including MAPK, PI3K/AKT, and Ras.
Conclusions: This study identified promising FGFR2 inhibitors, particularly Rutecarpine, as potential therapeutic candidates for cholangiocarcinoma, warranting further experimental validation.
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