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ALOX15, also known as arachidonic acid 15-lipoxygenase, promotes ferroptosis by converting intracellular unsaturated lipids into oxidized lipid intermediates and is an important ferroptosis target. In this study, a naive Bayesian machine learning classifier with a structure-based, high-throughput screening approach and a molecular docking program were combined to screen for three compounds with excellent target-binding potential. In the absorption, distribution, metabolism, excretion, and toxicity characterization, three candidate molecules were predicted to exhibit drug-like properties. The subsequent molecular dynamics simulations confirmed their stable binding to the targets. The findings indicated that the compounds exhibited excellent potential ALOX15 inhibitor capacity, thereby providing novel candidates for the treatment of inflammatory ischemia-related diseases caused by ferroptosis.<\/jats:p>","DOI":"10.3390\/ph15111440","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:05:11Z","timestamp":1668999911000},"page":"1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of Novel Arachidonic Acid 15-Lipoxygenase Inhibitors Based on the Bayesian Classifier Model and Computer-Aided High-Throughput Virtual Screening"],"prefix":"10.3390","volume":"15","author":[{"given":"Yinglin","family":"Liao","sequence":"first","affiliation":[{"name":"The First Clinical College, Guangdong Medical University, Zhanjiang 524023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-9713","authenticated-orcid":false,"given":"Lianxiang","family":"Luo","sequence":"additional","affiliation":[{"name":"The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China"},{"name":"The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2716","DOI":"10.1038\/cddis.2017.133","article-title":"Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells","volume":"8","author":"Basit","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/s41419-019-2064-5","article-title":"ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation","volume":"10","author":"Park","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3389\/fphar.2018.01371","article-title":"RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer","volume":"9","author":"Sui","year":"2018","journal-title":"Front. 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