{"refrec":{"BRefID":352761,"RR":"<b>Copmans, D.; Kildgaard, S.; Roux, E.; Partoens, M.; Steurs, G.; Wang, X.; De Borggraeve, W.M.; Esguerra, C.V.; Crawford, A.D.; Larsen, T.O.; de Witte, P.A.M.</b> (2022). From the North Sea to drug repurposing, the antiseizure activity of halimide and plinabulin. <i>Pharmaceuticals 15(2)</i>: 247. <a href=\"https://dx.doi.org/10.3390/ph15020247\" target=\"_blank\">https://dx.doi.org/10.3390/ph15020247</a>","BEntID":350470,"PublicFlag":1,"CheckedFlag":1,"wosflag":1,"vabbflag":0,"RefStringPartII":". <i>Pharmaceuticals 15(2)</i>: 247. <a href=\"https://dx.doi.org/10.3390/ph15020247\" target=\"_blank\">https://dx.doi.org/10.3390/ph15020247</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Copmans, D.; Kildgaard, S.; Roux, E.; Partoens, M.; Steurs, G.; Wang, X.; De Borggraeve, W.M.; Esguerra, C.V.; Crawford, A.D.; Larsen, T.O.; de Witte, P.A.M.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Copmans, D. <i>et al.</i>","Englishabstract":"PharmaSea performed large-scale in vivo screening of marine natural product (MNP) extracts, using zebrafish embryos and larvae, to identify compounds with the potential to treat epilepsy. In this study, we report the discovery of two new antiseizure compounds, the 2,5-diketopiperazine halimide and its semi-synthetic analogue, plinabulin. Interestingly, these are both known microtubule destabilizing agents, and plinabulin could have the potential for drug repurposing, as it is already in clinical trials for the prevention of chemotherapy-induced neutropenia and treatment of non-small cell lung cancer. Both halimide and plinabulin were found to have antiseizure activity in the larval zebrafish pentylenetetrazole (PTZ) seizure model via automated locomotor analysis and non-invasive local field potential recordings. The efficacy of plinabulin was further characterized in animal models of drug-resistant seizures, i.e., the larval zebrafish ethyl ketopentenoate (EKP) seizure model and the mouse 6 Hz psychomotor seizure model. Plinabulin was observed to be highly effective against EKP-induced seizures, on the behavioral and electrophysiological level, and showed activity in the mouse model. These data suggest that plinabulin could be of interest for the treatment of drug-resistant seizures. Finally, the investigation of two functional analogues, colchicine and indibulin, which were observed to be inactive against EKP-induced seizures, suggests that microtubule depolymerization does not underpin plinabulin’s antiseizure action.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"From the North Sea to drug repurposing, the antiseizure activity of halimide and plinabulin","OrigTitleLangCode":"en","OrigTitleLangCodeExtended":"eng","OrigTitleLangID":15,"DateLastModified":{"date":"2024-12-10 01:33:17.368041","timezone_type":1,"timezone":"+01:00"},"UserAccessRight":null,"UserAccID":null,"AuthorKeywords":"marine natural products; drug discovery; epilepsy; zebrafish; plinabulin; halimide","OtherDescriptors":null,"Notes":null,"AnaPub":2022,"MonPub":null,"DateUpdate":"2022-10-06","DateCreate":"2022-06-21","SecASFANote":null,"ConfID":null,"PeerRev":1,"VlizCoreFlag":1,"WoScode":"WOS:000775438900001","VABBcode":null,"OpenAcc":1,"DOI":"10.3390/ph15020247"},"refs":null,"anarec":{"AnaID":352761,"PubliDate":2022,"Pagination":"247","XtraPublOfAnaID":null,"ISBN":null,"Volume":"15","Issue":"2","BRefMon":null,"BRefMonRR":null,"BRefXtra":null,"BRefXtraRR":null,"SerBRefID":338260,"SerRR":"Pharmaceuticals. MDPI: Basel.  e-ISSN 1424-8247","StandardTitleSer":"Pharmaceuticals","ISSN":null,"AbbrevSer":null,"StandardTitleMon":null,"StartPage":26,"Pages":null,"ToPubliDate":null,"BRefBibLvlCode":"S","SerNotes":null},"monrec":null,"serrec":null,"relations":null,"relationsRev":null,"addrec":null,"othpubs":null,"ownerships":null,"authors":[{"AutName":"Copmans","Firstname":"Daniëlle","Initials":"D.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":318814,"OrderNr":1,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":"0000-0002-9804-8410","PersID":38767,"InsID":14389},{"AutName":"Kildgaard","Firstname":"Sara","Initials":"S.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407528,"OrderNr":2,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Roux","Firstname":"Emma","Initials":"E.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":489801,"OrderNr":3,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":"0000-0003-2629-6316","PersID":41202,"InsID":14389},{"AutName":"Partoens","Firstname":"Michèle","Initials":"M.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407532,"OrderNr":4,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":null,"PersID":38770,"InsID":14389},{"AutName":"Steurs","Firstname":"Gert","Initials":"G.","Affiliation":"Molecular Design and Synthesis, Department of Chemistry, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":489803,"OrderNr":5,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"Katholieke Universiteit Leuven; Departement Chemie; Afdeling Moleculair design en synthese","ORCID":"0000-0002-9779-7743","PersID":41203,"InsID":502},{"AutName":"Wang","Firstname":"Xinhui","Initials":"X.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":489804,"OrderNr":6,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"De Borggraeve","Firstname":"Wim","Initials":"W.M.","Affiliation":"Molecular Design and Synthesis, Department of Chemistry, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":368031,"OrderNr":7,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"Katholieke Universiteit Leuven; Departement Chemie; Afdeling Moleculair design en synthese","ORCID":"0000-0001-7813-6192","PersID":37236,"InsID":502},{"AutName":"Esguerra","Firstname":"Camila","Initials":"C.V.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407533,"OrderNr":8,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":"0000-0002-2271-8094","PersID":26998,"InsID":14389},{"AutName":"Crawford","Firstname":"Alexander","Initials":"A.D.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407535,"OrderNr":9,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":null,"PersID":38771,"InsID":14389},{"AutName":"Larsen","Firstname":"Thomas","Initials":"T.O.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407537,"OrderNr":10,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"de Witte","Firstname":"Peter","Initials":"P.A.M.","Affiliation":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven","Discriminator":null,"CorporateFlag":0,"BEntID":350470,"AutID":407538,"OrderNr":11,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Moleculaire Bio-ontdekking","ORCID":"0000-0002-9989-9567","PersID":38773,"InsID":14389}],"mapdetails":null,"datasets":null,"monographs":null,"monparts":null,"serparts":null,"BEntOpen":null,"BEntPrivate":null,"availability":[{"BInstID":378100,"LibID":36,"BRefID":352761,"EmbargoDate":null,"FullEmbargoDate":null,"PhysMedID":16,"hasOCRd":1,"ShelfLocCode":"378100","RFID":null,"PaidValue":null,"Medium":"Server","Description":"VLIZ Open Access","Acronym":"VLIZ","Library":"Vlaams Instituut voor de Zee","DutchTerm":"Open access","URL":null,"ClassifID":53,"Classification":"Open access","ReqLink":null,"ClassifTypID":1,"URLLocation":"https://www.vliz.be/imisdocs/publications/","SubDir":null,"InternalReq":0,"LoggedInReq":0,"Disclaimer":null,"DutchDisclaimer":null,"FileFormat":".pdf","FileDescr":"pdf","InsPub":1,"InsID":36,"FileFormID":6,"LendableFlag":1,"PublicFlag":1,"orderLib":"A","Notes":null,"AccConID":null,"AccessConstraint":null,"LicURL":null}],"litstyles":null,"thespers":null,"arch2discl":null,"SERpubls":[{"PublName":"MDPI","City":"Basel"}],"MONpubls":null,"pictures":[],"thestermsPath":null,"thestermsASFA":null,"taxtermsASFA":[{"TaxTerm":"Danio rerio"}],"geotermsASFA":null,"collections":[{"Collection":"OMA - Open Marien Archief","ShortName":"OMA"}],"conf":null,"proj":null,"Physdatasets":null,"spcols":{"222":{"SpName":"BMB - Belgische Mariene Bibliografie","SpColID":222,"ParSpColID":null,"TopParID":null,"ShortName":"BMB","URLLocation":null,"LibID":36,"OpenRepoFlag":null,"SpTypID":null,"TopParIDNotWebsite":null,"SpColPath":"BMB"},"221":{"SpName":"OMA - Open Marien Archief","SpColID":221,"ParSpColID":null,"TopParID":null,"ShortName":"OMA","URLLocation":null,"LibID":36,"OpenRepoFlag":1,"SpTypID":null,"TopParIDNotWebsite":null,"SpColPath":"OMA"}},"doi":null,"publs":null,"serparttypes":null,"monauthors":null,"MParts":null,"SParts":null,"hLibs":null,"langs":[{"BEntID":350470,"AbstractFlag":0,"LangID":15,"LangCode":"en","Lang":"English","DutchTerm":"Engels","LangCodeExtended":"eng"},{"BEntID":350470,"AbstractFlag":1,"LangID":15,"LangCode":"en","Lang":"English","DutchTerm":"Engels","LangCodeExtended":"eng"}],"urls":[{"URL":"https://dx.doi.org/10.3390/ph15020247","externalID":"10.3390/ph15020247","URLTypeCode":"DOI","URLID":103445,"URLTypID":13,"URLType":"DOI","URLPrefix":"http://dx.doi.org/"}],"thesterms":null,"taxterms":[{"TaxTerm":"Danio rerio","AphiaID":1026595,"TaxtID":23079}],"geoterms":null,"othterms":null,"asfacodes":null,"asfa2codes":null,"thestermsFRIS":null,"taxtermsFRIS":[{"TaxTerm":"Danio rerio","DutchTerm":null,"AphiaID":1026595,"TaxtID":23079}],"geotermsFRIS":null,"othtermsFRIS":null,"resmessage":"","complete":1,"sessions":{"newSesName":"Bouchti, Zohra, Z.","newSesDate":{"date":"2022-06-21 10:37:05.430000","timezone_type":3,"timezone":"Europe/Brussels"},"updSesName":"Bouchti, Zohra, Z.","updSesDate":{"date":"2022-10-06 08:00:35.350000","timezone_type":3,"timezone":"Europe/Brussels"}}}