{"id":16438,"date":"2024-11-05T15:35:07","date_gmt":"2024-11-05T15:35:07","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=16438"},"modified":"2024-11-05T15:35:07","modified_gmt":"2024-11-05T15:35:07","slug":"2024-discovery-of-a-potent-kv7-3-selective-potassium-channel-opener-from-a-polynesian-traditional-botanical-anticonvulsant","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-discovery-of-a-potent-kv7-3-selective-potassium-channel-opener-from-a-polynesian-traditional-botanical-anticonvulsant\/","title":{"rendered":"2024 &#8211; Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant"},"content":{"rendered":"<p>Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (K<sub>v<\/sub>) channel formed by K<sub>v<\/sub>7.2\/3 (KCNQ2\/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate K<sub>v<\/sub>7.2\/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified\u00a0<i>Thespesia populnea<\/i>\u00a0(<i>miro, milo<\/i>, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated K<sub>v<\/sub>7.2\/3 (EC<sub>50<\/sub>, 2.8\u2009nM). GA is, uniquely to our knowledge, 100% selective for K<sub>v<\/sub>7.3 versus other Kv7 homomers; it requires S5 residue K<sub>v<\/sub>7.3-W265 for K<sub>v<\/sub>7.2\/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized K<sub>v<\/sub>7.2\/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of\u00a0<i>T. populnea<\/i>\u00a0as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic K<sub>v<\/sub>7 channel activation.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[143],"target_categories":[61],"target_families":[333],"targets":[455],"resource_keyword":[],"class_list":["post-16438","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv7-3"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/16438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=16438"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=16438"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=16438"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=16438"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=16438"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=16438"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=16438"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=16438"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=16438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}