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To address this, the present study employed network\u2010based analysis using protein\u2010protein interaction (PPI)\u00a0data to identify hub proteins and their functional insights. We constructed a PPI network consisting of 1413 dysregulated genes in TNBC. These hub genes displayed 5763 interactions. The downstream analysis identified TP53, SRC, EP300, AKT1, HSP90AA1, MAPK3, EGFR, and SMAD3 as hub proteins based on topological parameters and functional enrichment analyses. The DGIdb data were exploited to investigate the link between drugs and the identified hub genes. Collectively, the findings showed that no Food and Drug Administration (FDA)\u2010approved drugs exist to target the EP300 protein. This situation necessitates the discovery of potential repurposed candidate against EP300 protein from the repository of 2147 FDA\u2010approved compounds. Precisely, molecular docking, MM\u2010GBSA, and ML\u2010based rescoring analysis identified DB06137 (tirbanibulin) as a lead compound. Moreover, the dynamic behavior of DB06137 reinforces its exceptional structural stability with EP300, indicating its potential for novel therapeutic applications. We hypothesize that tirbanibulin interacts either with the regulatory regions of EP300 through allosteric inhibition or indirectly by altering upstream signaling pathways. Given the vital role of drug repurposing, experimental investigations on tirbanibulin unanticipated effects against EP300 are an interesting future direction.<\/jats:p>","DOI":"10.1002\/bab.70039","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:55:08Z","timestamp":1755150908000},"page":"1000-1007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the Complexities in TNBC Gene Interaction Networks Towards Better Therapeutics"],"prefix":"10.1002","volume":"73","author":[{"given":"Priyanga","family":"Paranthaman","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Bio Sciences and Technology Vellore Institute of Technology  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HemaNandini Rajendran","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bio Sciences and Technology Vellore Institute of Technology  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvakumar","family":"Veluchamy","sequence":"additional","affiliation":[{"name":"Computer Science and Engineering, P.S.R. 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