Using systems biology and drug repositioning approaches to discover FDA-approved drugs candidates for endometriosis treatment

Abstract

Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity. The administration of drugs designated for this condition has significant adverse effects, such as signs of estrogen insufficiency and suppression of ovulation. Considering this issue, this study aims to employ drugs repurposing approaches for the treatment of endometriosis. The GSE120103 dataset was selected to assess the expression of genes involved in endometriosis, then differentially expressed genes (DEGs) were identified using the “Limma” package in R Studio. Functional and pathway enrichment analysis of 708 up-regulated and 414 down-regulated DEGs was performed using ShinyGO 0.81 and DAVID tools. the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was then used to build a protein-protein interaction (PPI) network of up-regulated DEGs, followed by Cytoscape software to identify hub genes. Vascular endothelial growth factor receptor 2 (VEGFR2) and interleukin-6 (IL-6) were identified as hub genes, assessments suggested that VEGFR2 may be a more promising possibility for druggability than IL-6. 16 FDA-approved drugs targeting VEGFR2 were identified, and molecular docking analysis indicated that ponatinib (−9.6 kcal/mol) had a more favorable binding energy than the co-crystal ligand (−9.2 kcal/mol). Moreover, molecular dynamics (MD) simulation analysis demonstrated considerable stability of the VEGFR2-ponatinib complex over a 100 nanoseconds (ns) timescale. The findings of this study indicate that ponatinib may provide considerable therapeutic promise for the treatment of endometriosis. Nevertheless, additional experimental investigations are required to evaluate its therapeutic efficacy.