{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:16:17Z","timestamp":1785244577820,"version":"3.55.0"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 (TRESK) displays one of the most unusual two pore domain potassium channels, that is associated with different neurological and immune\u2010related diseases emphasizing the therapeutic potential of K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 activators. Previous studies identified cloxyquin and nitroxoline as lead compounds that do not alter the function of other K\n                    <jats:sub>2P<\/jats:sub>\n                    channels. Although their 8\u2010OH group is crucial for channel activation, 8\u2010hydroxyquinolines are known for various effects including metal chelation and antibacterial properties increasing the risk of side effects. Therefore, we synthesized 14 quinoline derivatives to search for other tolerated substitutions in 8\u2010position. Activity determination using two\u2010electrode voltage clamp (TEVC) revealed that four derivatives achieved moderate inhibitory or stimulatory activity. Among these, benzaldimine\n                    <jats:bold>3d<\/jats:bold>\n                    represents a new extended scaffold that unexpectedly increases K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 channel activity by about 60% at 100\u2009\u00b5M. Docking studies suggest that despite the enlarged structure,\n                    <jats:bold>3d<\/jats:bold>\n                    is still able to achieve in silico interactions with important amino acids from the cloxyquin binding site. However, its usability in vitro is limited by hydrolysis leading to a compound half\u2010life of 39\u2009min in aqueous solutions. Nevertheless, the identification of a possible scaffold extension for K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 channel activators opens a new opportunity for future compound diversification.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70310","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:53:07Z","timestamp":1784181187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Novel Cloxyquin Analogs for K\n                    <sub>2P<\/sub>\n                    18.1 Channel Modulation"],"prefix":"10.1002","volume":"359","author":[{"given":"Jasmin","family":"S\u00f6rgel","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3737-2164","authenticated-orcid":false,"given":"Marcel","family":"Kloth","sequence":"additional","affiliation":[{"name":"Organisch\u2010Chemisches Institut University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-5969","authenticated-orcid":false,"given":"Henning","family":"Klaasen","sequence":"additional","affiliation":[{"name":"Organisch\u2010Chemisches Institut University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-3501","authenticated-orcid":false,"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8183","authenticated-orcid":false,"given":"Thomas","family":"Budde","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-7485","authenticated-orcid":false,"given":"Bart Jan","family":"Ravoo","sequence":"additional","affiliation":[{"name":"Organisch\u2010Chemisches Institut University of M\u00fcnster  M\u00fcnster NRW Germany"},{"name":"Center for Soft Nanoscience University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-7539","authenticated-orcid":false,"given":"Julian A.","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  M\u00fcnster NRW Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-032-07523-9_8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522459113"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.11.039"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51288-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2021_460"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.12"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000589"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206810200"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602495200"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-33992-7"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP279203"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00629.2005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109404"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00170"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17978-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14081992"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aao5150"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz342"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-020-02382-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00580-z"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136376"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.10.090"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.09.093"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00010"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13821"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-1188598\/v1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123091"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2016.03.014"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S49763"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05114-4"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.1702"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.9b00942"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo400949p"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1ob00260k"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol3005613"},{"key":"e_1_2_10_37_1","unstructured":"M.Llinas\u2010Brunet M. D.Bailey D.Cameron et al. Hepatitis C Inhibitor Peptides WO\/2000\/009558 2000."},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c03780"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/c6nj03793c"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b02306"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1705892"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2006.10.007"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5sc01208b"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1588420"},{"key":"e_1_2_10_45_1","unstructured":"D.Reynolds M. W.Seiler A. A.Agrawal F.Vaillancourt andP.Smith \u201cCompounds and Methods for Modulating Splicing \u201d WO\/2021\/174164."},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.004"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201209885"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo026850"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.115626"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62099-w"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48922-w"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.3c02939"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0022476619110064"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.24346"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.02.042"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm950732f"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1039\/dt9810002063"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1039\/cs9770600063"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.166995"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.11.017"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu426"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20921"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.70310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:56:07Z","timestamp":1785243367000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":61,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/ardp.70310"],"URL":"https:\/\/doi.org\/10.1002\/ardp.70310","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70310"}}