{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:37:21Z","timestamp":1785418641695,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-33\/2026-03\/200017"],"award-info":[{"award-number":["451-03-33\/2026-03\/200017"]}]},{"award":["451-03-33\/2026-03\/200017"],"award-info":[{"award-number":["451-03-33\/2026-03\/200017"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The primary control mechanism for synaptic uptake of GABA is through \u03b3-aminobutyric acid transporter 1 (GAT-1, SLC6A1), a known target for anti-epileptic drugs. Although there is a clinically used GAT-1 inhibitor, tiagabine, the development of a new ligand with an advanced pharmacological profile is desirable. For this purpose, a multi-tiered virtual approach to screening has been created, involving pharmacophore-based search; application of the Informational Spectrum Method for Small Molecules, followed by EIIP\/AQVN filtering (ISM-SM); molecular docking using an ensemble of several experimentally obtained structures of GAT-1; and ADMET predictions. Pharmacophore-based screening of the ZINC database of natural products, combined with ISM-SM\/EIIP filtering, yielded 237 candidate compounds. Structural separation analysis discriminated between the positives and negatives, enabling enrichment-based prioritization. The use of a composite normalized rank score based on docking affinity and structural similarity allowed for the identification of the top candidates: ZINC03643214 and ZINC67840571. Collectively, these refinements establish a more sophisticated computational model for identifying novel GAT-1 inhibitors and highlight promising candidates for future experimental evaluation.<\/jats:p>","DOI":"10.3390\/ph19071011","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:27:37Z","timestamp":1782746857000},"page":"1011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Selection of GAT-1 Inhibitors"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7066-426X","authenticated-orcid":false,"given":"Kristina","family":"Stevanovic","sequence":"first","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"},{"name":"Theory Department, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Perovic","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-1055","authenticated-orcid":false,"given":"Sanja","family":"Glisic","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-3223","authenticated-orcid":false,"given":"Milan","family":"Sencanski","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1007\/s11064-014-1263-9","article-title":"The GABA Synapse as a Target for Antiepileptic Drugs: A Historical Overview Focused on GABA Transporters","volume":"39","author":"Schousboe","year":"2014","journal-title":"Neurochem. 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