@article{article_1696839, title={Maprotiline as a Repositioned Drug Candidate for the Treatment of Non-Functioning Pituitary Neuroendocrine Tumors: a Network-Based Omics-Oriented Approach}, journal={International Journal of Advances in Engineering and Pure Sciences}, volume={37}, pages={418–428}, year={2025}, DOI={10.7240/jeps.1696839}, author={Aydın, Büşra}, keywords={transkriptomik, RNA dizileme, biyolojik ağlar, ilaç repozisyonu, hipofiz nöroendokrin tümörler}, abstract={Non-functioning pituitary neuroendocrine tumors pose a great challenge not only for the clinic but also for patients since it has an insidious progression. Even though effortful studies and state-of-the-art techniques are improving our knowledge about this disease, no therapeutic modality is currently approved for the treatment. This study aimed to determine significantly altered genes that showed aberrantly expressed patterns in NF-PitNET using high-throughput RNA-sequencing transcriptome data. To uncover essential elements in disease pathogenesis, biological networks in protein, transcription factor, and microRNA levels were constructed and topologically analyzed. by drug prioritization for NF-PitNETs via a repositioning approach. The hub elemets of AGO2, BCL2L2, BIRC5, BRCC3, CDC42, CUL3, E2F2, ESR1, ESR2, GIGYF1, JUN, KRAS, MDM2, NFKB1, PLEKHA4, RELA, RNF40, and ZNF460 were proposed as systems biomarkers of NF-PitNET. A signature-based drug repositioning using hub elements as treatment targets unraveled repositioned drug candidates including valdecoxib, penfluridol, maprotiline, mitoxantrone, vorinostat, homoharringtonine, norethynodrel, strophantine octahydrate, bufalin, and digoxin. The efficiency of maprotiline was confirmed in silico via molecular docking and resulted in higher binding affinities with hub elements compared to their inhibitors. Maprotiline was proposed as a promising repositioned therapeutic for the management of NF-PitNETs.}, number={3}, publisher={Marmara Üniversitesi}, organization={Not available.}