{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:42:28Z","timestamp":1790131348591,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["12345"],"award-info":[{"award-number":["12345"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We searched for, from the FDA (Food and Drug Administration\u2010USA)\u2010approved drugs, inhibitors of <jats:italic>FKBP5<\/jats:italic> with tolerable adverse effect profiles (eg, mild headache, sedation, etc.) and with the ability to cross the blood brain barrier (BBB), using bio\u2010informatics tools (in\u2010silico). This may pave the road for designing clinical trials of such drugs in patients with functional seizures (FS) and other stress\u2010associated disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Several databases were used to find all the approved drugs that potentially have interactions with FKBP51 protein [ie, CTD gene\u2010chemical interaction section of FKBP51 protein of Harmonizome of Mayaanlab, DrugCenteral database, PDID (Protein Drug Interaction Database), DGIdb (the Drug Gene Interaction database)]. Other databases were also searched [eg, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>; DRUGBANK (the FASTA format of the FKBP51 protein was imported to the target sequencing section of the database to find the associated drugs), and the STITCH database (to find the related chemical interaction molecules)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After a comprehensive search of the designated databases, 28 unique and approved drugs were identified. Fluticasone propionate and Mifepristone and Ponatinib, Mirtazapine, Clozapine, Enzalutamide, Sertraline, Prednisolone, Fluoxetine, Dexamethasone, Clomipramine, Duloxetine, Citalopram, Chlorpromazine, Nefazodone, and Escitalopram are inhibitors of FKBP5 and have BBB permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>While the current in\u2010silico repurposing study could identify potential drugs (that are already approved and are widely available) for designing clinical trials in patients with stress\u2010associated disorders (eg, FS), any future clinical trial should consider the pharmacological profile of the desired drug and also the characteristics and comorbidities of the patients in order to foster a success.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12749","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T08:10:14Z","timestamp":1681978214000},"page":"633-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<i>FKBP5<\/i> blockade may provide a new horizon for the treatment of stress\u2010associated disorders: An in\u2010silico study"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-7601","authenticated-orcid":false,"given":"Ali A.","family":"Asadi\u2010Pooya","sequence":"first","affiliation":[{"name":"Epilepsy Research Center Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Department of Neurology, Jefferson Comprehensive Epilepsy Center Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Malekpour","sequence":"additional","affiliation":[{"name":"Epilepsy Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bardia","family":"Zamiri","sequence":"additional","affiliation":[{"name":"Epilepsy Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Kashkooli","sequence":"additional","affiliation":[{"name":"Epilepsy Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Firouzabadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2013.11.005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2021.1942870"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2007.04.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.235424"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2009.06.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060513496170"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063850"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.05.006"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-309390"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108085"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.06.024"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107534"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009855"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(20)30128-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.235"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2017.08.066"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpsp.12198"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-019-03887-3"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04315-7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12716"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02394.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw100"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa997"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv597"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1084"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj067"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1277"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2269-7_19"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci300367a"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1075"},{"key":"e_1_2_11_34_1","unstructured":"Drugs.com.Drug Side Effects.www.Drugs.com\/sfx. Accessed December 4 2021."},{"key":"e_1_2_11_35_1","unstructured":"Mifeperex (mifepristone) Information. FDA.https:\/\/www.fda.gov\/drugs\/postmarket\u2010drug\u2010safety\u2010information\u2010patients\u2010and\u2010providers\/mifeprex\u2010mifepristone\u2010information\/. Accessed September 1 2021."},{"key":"e_1_2_11_36_1","unstructured":"DRUGBANK.Fluticasoe propionate information. [updated Drug created on June 13 2005 13:24\/Updated on October 3 2021 00:39].https:\/\/go.drugbank.com\/drugs\/DB00588. Accessed September 1 2021."},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.02.006"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00065"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04891-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.014"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.12.037"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.817"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02326-2"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5332-09.2010"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-12-2-118"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1699"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T04:59:27Z","timestamp":1692507567000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,27]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/epi4.12749"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12749","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,27]]},"assertion":[{"value":"2023-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}