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Page 421 Aydin et al. J Transl Genet Genom. 2025;9:406-26 https://dx.doi.org/10.20517/jtgg.2025.108

muscle. This targeted emphasis may overlook compounds with activation potential capable of restoring
pathways related to muscle regeneration, mitochondrial bioenergetics, or metabolic homeostasis. The
restricted scope of screening may therefore underrepresent the therapeutic potential of drugs that act
through upregulatory mechanisms. The molecular docking simulations provide structural insight into
potential ligand-protein interactions; however, docking remains an approximation that does not account for
conformational flexibility, dynamic cellular environments, pharmacokinetic constraints, or drug
metabolism. Protein dynamics, post-translational modifications, and tissue-specific isoforms may influence
binding in vivo in ways that cannot be fully represented through static docking models.

Despite these limitations, the study establishes a coherent computational framework capable of uncovering
biologically meaningful targets and generating testable hypotheses for therapeutic development. The
integration of network biomarkers, transcriptomic perturbation signatures, and ligand-target affinity
modeling provides a foundation for future investigations that combine in silico predictions with cellular and
animal validation studies. A key direction for subsequent work involves confirming whether the in silico
predictions translate into measurable phenotypic improvements in experimental DMD models and
exploring whether activation-based therapeutics could complement the inhibitory mechanisms identified
here.

CONCLUSION
DMD is a rare and challenging disease, as there is no complete cure. In this study, omics-oriented network
constructions were performed to integrate transcriptome-level data and multi-omic crosstalk in the
pathogenesis of DMD. The identified biomarkers were used as targets to reverse the gene expression
signatures of DMD via drug repositioning. Two repositioned drug candidates, emetine dihydrochloride
hydrate and celastrol, were reported as potential therapeutic agents for the management of DMD. Emetine
dihydrochloride hydrate, a potent plant-derived alkaloid, and celastrol, a bioactive compound derived from
plants, exhibited promising pharmacological properties according to docking results. These findings
demonstrate the significant therapeutic potential of these phytochemical-derived compounds and reinforce
the importance of phytochemicals as a foundation for novel drug development in modern medicine.

DECLARATIONS
Authors’ contributions
Made substantial contributions to drafting the work, methodology, and visualization: Parmak HB, İyisoy
ME, Unal Z, Eskicubuk H
Made substantial contributions to methodology, software development, data curation, and visualization:
Okutan K
Made substantial contributions to conceptualization, methodology, validation, software development, data
curation, visualization, supervision, and writing - review & editing: Aydin B.
All authors contributed to the original draft and approved the final version of the manuscript.

Financial support and sponsorship
Not applicable.

Availability of data and materials
The datasets used in this study are publicly available in the Gene Expression Omnibus (GEO) database at
the following links: GSE38417- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38417,
GSE109178- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109178, GSE70955- https://www.
ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70955. Additional data related to this study are available from