Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Abstract

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.