{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:01:44Z","timestamp":1785142904061,"version":"3.55.0"},"reference-count":69,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heterotetrameric K\n                    <jats:sub>V<\/jats:sub>\n                    7.2\/3 potassium channels were retrospectively identified as the target of the analgesic flupirtine and the antiepileptic retigabine (ezogabine). Clinical utility of these agents ended after decades or 6 years, respectively, before their full scope was explored. Market withdrawals in 2017 and 2018 hampered research in other medical fields and left a gap for researchers using these compounds off\u2010label in experimental indications and for patients with K\n                    <jats:sub>V<\/jats:sub>\n                    7.2\/3 malfunctions. Failure of these drugs might be regarded as a reason to abandon this class of compounds, due to the notion that toxicity might be a class effect and to competitive markets. Yet, evidence accumulated that the toxicity of both compounds is not an inherent property of modulators of K\n                    <jats:sub>V<\/jats:sub>\n                    7.2\/3 channels, but rather the result of an oxidation\u2010sensitive metabophore\/toxicophore. Second, epilepsy associated with K\n                    <jats:sub>V<\/jats:sub>\n                    7.2\/3 channelopathies might rationally be addressed best with modulators of this validated drug target. Employing retrometabolic drug design to remodel the enzyme\u2010labile carbamate structure and the central highly substituted ring, azetukalner (formerly encukalner, XEN1101) emerged from the unlucky forerunners. This structural analog of retigabine exhibits improved metabolic stability, increased potency, and enhanced blood\u2013brain barrier penetration compared with its predecessor. This review details the synthesis, physicochemical properties, and clinical results of azetukalner.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70279","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:54:31Z","timestamp":1783079671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Retigabine to Azetukalner: Reviving Voltage\u2010Gated Potassium Channels for Epilepsy Therapy"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4745-3925","authenticated-orcid":false,"given":"Pascal","family":"Rosendahl","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry, Institute of Pharmacy University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-3395","authenticated-orcid":false,"given":"Lukas","family":"Schulig","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry, Institute of Pharmacy University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1262-6636","authenticated-orcid":false,"given":"Andreas","family":"Link","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry, Institute of Pharmacy University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.679317"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00688"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-024-01155-3"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.570588"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1087-9"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04138.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2013.8895"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098614560736"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106580"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000211240"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70334"},{"key":"e_1_2_11_14_1","unstructured":"Shanghai 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