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However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore this mechanism based on network pharmacology and molecular docking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Six and two databases were used to identify targets associated with clozapine and agranulocytosis, respectively. The bioinformatics online platform was used to identify overlaps between the drug and disease targets. The protein\u2013protein interaction (PPI) network was characterized using Cystoscope 3.10.1 and STRING. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were analyzed using the DAVID online platform. A drug\u2010target\u2010pathway\u2010disease network was constructed utilizing Cystoscope 3.10.1. The Auto Dock Vina and PyMOL software were used to verify the molecular docking of clozapine and core targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis revealed 188 overlapping targets. The PPI and KEGG enrichment pathway analyses demonstrated that clozapine induces agranulocytosis by modulating the hematopoietic cell lineage and JAK\u2013STAT signaling pathways via interleukin\u20103 (IL3), IL6, IL2 receptor subunit alpha (IL2RA), and granulocyte colony\u2010stimulating factor. Binding energies between clozapine and core targets were favorable (&lt;\u2009\u22127.0\u2009kcal\/mol).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Clozapine\u2010induced agranulocytosis may be linked to the JAK\u2013STAT inflammatory signaling pathway through inflammatory and hematopoietic\u2010related cytokines. Our findings enhance our comprehension of the potential mechanisms underlying clozapine\u2010induced agranulocytosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70206","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T09:53:31Z","timestamp":1736330011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK\u2013STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking"],"prefix":"10.1111","volume":"31","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Computational Biology Center, Tianjin Anding Hospital Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University  Tianjin China"},{"name":"Department of Psychiatry and Psychology, School of Basic Medical Sciences Tianjin Medical 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