{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:54:05Z","timestamp":1781585645470,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010NS096976"],"award-info":[{"award-number":["R01\u2010NS096976"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010HD102071"],"award-info":[{"award-number":["R01\u2010HD102071"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21\u2010NS138525"],"award-info":[{"award-number":["R21\u2010NS138525"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54\u2010NS117170"],"award-info":[{"award-number":["U54\u2010NS117170"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000095","name":"Savoy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Syntaxin\u2010binding protein 1 (\n                    <jats:italic>STXBP1<\/jats:italic>\n                    ) mutations lead to severe epilepsy, intellectual disability, developmental delay, and movement disorder. Effective treatments for these conditions do not exist. Recent studies in Munc18\u20101 (\n                    <jats:italic>STXBP1<\/jats:italic>\n                    )\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    models demonstrate that 4\u2010phenylbutyrate (4\u2010PBA) or related pharmacological chaperones stabilize Munc18\u20101 protein levels and rescue locomotion deficits. These studies suggest a novel treatment strategy for these patients. Here, we used a\n                    <jats:italic>stxbp1a<\/jats:italic>\n                    zebrafish model with a profound movement disorder to screen 4\u2010PBA and alternative structural analogs identified using artificial intelligence (AI)\u2010based screening. Automated locomotion assays conducted on larval\n                    <jats:italic>stxbp1a<\/jats:italic>\n                    mutant zebrafish at 5\u2009days post\u2010fertilization (dpf) confirm and extend the movement disorder endophenotype. Drug treatment (4\u2010PBA or 16 identified candidates) failed to rescue the\n                    <jats:italic>stxbp1a<\/jats:italic>\n                    mutant zebrafish locomotion deficit. Electrophysiology studies in a\n                    <jats:italic>stxbp1b<\/jats:italic>\n                    zebrafish model characterized by spontaneous seizure activity (i.e., epilepsy) failed to detect a reduction in ictal\u2010like events with 4\u2010PBA treatment. Taken together, our results suggest caution in repurposing 4\u2010PBA or related compounds for the treatment of STXBP1 disorders.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70285","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:22:12Z","timestamp":1781104932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virtual Screening and Zebrafish Phenotype\u2010Based Evaluation Argues Against Repurposing 4\u2010Phenylbutyrate for\n                    <scp>STXBP1<\/scp>\n                    \u2010Related Disorders"],"prefix":"10.1002","volume":"14","author":[{"given":"Aline","family":"Frick","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery &amp; Weill Institute for Neuroscience University of California, San Francisco  San Francisco California USA"},{"name":"Faculty of Psychology and Neuroscience Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Whyte\u2010Fagundes","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery &amp; Weill Institute for Neuroscience University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-9781","authenticated-orcid":false,"given":"Scott C.","family":"Baraban","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery &amp; Weill Institute for Neuroscience University of California, San Francisco  San Francisco California USA"},{"name":"Helen Wills Institute of Neuroscience University of California, Berkeley  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105469"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11320"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23484"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15120"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002457"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.150"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02767.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12439"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000291"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000337"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.04.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad287"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-024-07783-3"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-41199-1_1"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae019"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06507-4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac144"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17779"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000249142.82285.d6"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-024-01371-1"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.06.24316676"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1469"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16849"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/154065802761001293"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00210-8"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01115-5"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12111"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2022.0541"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126647"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.3030490107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3410"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00996-2"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151148"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0066-17.2017"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054166"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.11.031"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2022.109594"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.4c01966"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12257-020-0049-y"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1459954"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107699"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11556"},{"key":"e_1_2_11_45_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.1141","article-title":"Improving Transparency and Scientific Rigor in Academic Publishing","volume":"9","author":"Prager E. M.","year":"2019","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0072-16.2016"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae135"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.70285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:19:59Z","timestamp":1781583599000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/prp2.70285"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70285","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70285"}}