{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:14:15Z","timestamp":1785255255481,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science &amp; Technology","doi-asserted-by":"publisher","award":["CRC-15-04-KIST"],"award-info":[{"award-number":["CRC-15-04-KIST"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pathogenesis of several neurodegenerative diseases such as Alzheimer\u2019s or Huntington\u2019s disease has been associated with metabolic dysfunctions caused by imbalances in the brain and cerebral spinal fluid levels of neuroactive metabolites. Kynurenine monooxygenase (KMO) is considered an ideal therapeutic target for the regulation of neuroactive tryptophan metabolites. Despite significant efforts, the known KMO inhibitors lack blood\u2013brain barrier (BBB) permeability and upon the mimicking of the substrate binding mode, are subject to produce reactive oxygen species as a side reaction. The computational drug design is further complicated by the absence of complete crystal structure information for human KMO (hKMO). In the current work, we performed virtual screening of readily available compounds using several protein\u2013ligand complex pharmacophores. Each of the pharmacophores accounts for one of three distinct reported KMO protein-inhibitor binding conformations. As a result, six novel KMO inhibitors were discovered based on an in vitro fluorescence assay. Compounds VS1 and VS6 were predicted to be BBB permeable and avoid the hydrogen peroxide production dilemma, making them valuable, novel hit compounds for further drug property optimization and advancement in the drug design pipeline.<\/jats:p>","DOI":"10.3390\/molecules26113314","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T21:42:06Z","timestamp":1622497326000},"page":"3314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacophore-Based Virtual Screening of Novel Competitive Inhibitors of the Neurodegenerative Disease Target Kynurenine-3-Monooxygenase"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-9746","authenticated-orcid":false,"given":"Lizaveta","family":"Gotina","sequence":"first","affiliation":[{"name":"Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Hee","family":"Seo","sequence":"additional","affiliation":[{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Min","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae Nim","family":"Pae","sequence":"additional","affiliation":[{"name":"Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.semcdb.2015.03.002","article-title":"The kynurenine pathway and neurodegenerative disease","volume":"40","author":"Maddison","year":"2015","journal-title":"Semin. 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