{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:59:36Z","timestamp":1785218376632,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["CUP E63C22001680001\u2014ID T4\u2010AN\u201004"],"award-info":[{"award-number":["CUP E63C22001680001\u2014ID T4\u2010AN\u201004"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ataxia\u2013Telangiectasia (AT) is a rare neurodegenerative disorder characterized by progressive neuronal loss and chronic neuroinflammation. Emerging evidence indicates that aberrant overexpression of the adaptor protein TYROBP promotes sustained recruitment and activation of spleen tyrosine kinase (SYK), contributing to pathogenic inflammatory signaling in AT. In this study, we applied a drug repositioning strategy to identify clinically approved compounds that inhibit SYK activity. An integrated\n                    <jats:italic>in silico<\/jats:italic>\n                    workflow was employed, combining convolutional neural network (CNN)\u2013based molecular docking with network medicine analysis using the SAveRUNNER platform to screen a library of 2342 FDA\u2010approved drugs. The top\u2010ranked candidates were further evaluated using long\u2010timescale molecular dynamics simulations and post\u2010simulation redocking to assess their binding stability and conformational persistence within the SYK catalytic pocket under explicit solvent conditions. This multilevel computational analysis identified vemurafenib and palbociclib as the most promising SYK inhibitors, both exhibiting sustained binding affinity and stable intermolecular interactions following protein relaxation. These findings support the feasibility of repurposing FDA\u2010approved drugs to modulate SYK\u2010driven neuroinflammatory pathways and provide a mechanistic framework for developing novel neuroprotective interventions for AT.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70354","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:02:06Z","timestamp":1782925326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Drug Repositioning Identifies\n                    <scp>SYK<\/scp>\n                    Kinase Inhibitors as Potential Neuroprotective Agents for Ataxia\u2013Telangiectasia"],"prefix":"10.1111","volume":"108","author":[{"given":"Alessia","family":"Romano","sequence":"first","affiliation":[{"name":"Department of Drug and Health Sciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Buccheri","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zagni","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rescifina","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010017\u20103677\u20107"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1493"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30163361"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1040"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/916240"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010015\u20100379\u20109"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859\u2010021\u201004076\u2010w"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3579"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403221"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010022\u201000552\u2010w"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.04.027"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.02.060"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113622"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583512000066"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010026\u201003840\u2010z"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010200161120\u201000007"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/03946320241282030"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197009"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw641"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321\u2010025\u201000973\u2010x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2765"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300687e"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3198"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2009.01.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1071\u20109091(03)00026\u20103"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184331"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051038"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.062745"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010016\u20100543\u20107"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00923"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12091370"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201271b"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2024.137764"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500696t"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2024.13228"}],"container-title":["Chemical 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