{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:17Z","timestamp":1790744537931,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) remains a major neurodegenerative disorder with limited therapeutic medication. Despite intensive efforts, the clinical development of \u03b2\u2010site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors has been hindered by off\u2010target effects, poor brain penetration, and toxicity, which is often due to a lack of selectivity over BACE2. In this study, we conducted a comprehensive analysis of over 9,000 reported BACE1 inhibitors to identify key physicochemical properties and interaction fingerprints associated with effective binding. These criteria were used to filter a library of 1.4 million commercially available compounds, prioritizing candidates with better safety and blood\u2010brain barrier (BBB) permeability properties. The top\u2010ranked molecules were evaluated through molecular docking and molecular dynamics (MD) simulations, followed by selectivity assessments against BACE2 and additional off\u2010targets. Among these, two compounds, MCULE\u20105138978734 and MCULE\u20102333131051, exhibited strong and stable binding to BACE1 with markedly reduced affinity for BACE2, suggesting improved selectivity. This integrative\n                    <jats:italic>in silico<\/jats:italic>\n                    framework demonstrates a rational strategy for the discovery of selective BACE1 inhibitors and highlights promising lead candidates for further experimental validation in the development of AD therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70169","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T07:13:02Z","timestamp":1759216382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rational Discovery of BACE1\u2010Selective Inhibitors as Potential Therapeutics for Alzheimer's Disease"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-0005","authenticated-orcid":false,"given":"Tanmaykumar","family":"Varma","sequence":"first","affiliation":[{"name":"Department of Pharmacoinformatics National Institute of Pharmaceutical Education and Research S.A.S. Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-9485","authenticated-orcid":false,"given":"Pradnya","family":"Kamble","sequence":"additional","affiliation":[{"name":"Department of Pharmacoinformatics National Institute of Pharmaceutical Education and Research S.A.S. Nagar Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-4809","authenticated-orcid":false,"given":"Prabha","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Pharmacoinformatics National Institute of Pharmaceutical Education and Research S.A.S. 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