{"id":6305,"date":"2023-02-17T06:57:01","date_gmt":"2023-02-17T06:57:01","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-discovery-of-a-small-molecule-modulator-of-the-kv1-1-kv%ce%b21-channel-complex-that-reduces-neuronal-excitability-and-in-vitro-epileptiform-activity\/"},"modified":"2023-02-17T06:57:01","modified_gmt":"2023-02-17T06:57:01","slug":"2019-discovery-of-a-small-molecule-modulator-of-the-kv1-1-kv%ce%b21-channel-complex-that-reduces-neuronal-excitability-and-in-vitro-epileptiform-activity","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2019-discovery-of-a-small-molecule-modulator-of-the-kv1-1-kv%ce%b21-channel-complex-that-reduces-neuronal-excitability-and-in-vitro-epileptiform-activity\/","title":{"rendered":"2019 &#8211; Discovery of a small molecule modulator of the KV1.1\/KV\u03b21 channel complex that reduces neuronal excitability and in vitro epileptiform activity"},"content":{"rendered":"<p>Aims: KV1.1 (KCNA1) channels contribute to the control of neuronal excitability and have been associated with epilepsy. KV1.1 channels can associate with the cytoplasmic KV\u03b21 subunit resulting in rapid inactivating A\u2010type currents. We hypothesized that removal of channel inactivation, by modulating KV1.1\/KV\u03b21 interaction with a small molecule, would lead to decreased neuronal excitability and anticonvulsant activity. Methods: We applied high\u2010throughput screening to identify ligands able to modulate the KV1.1\u2010T1 domain\/KV\u03b21 protein complex. We then selected a compound that was characterized on recombinant KV1.1\/KV\u03b21 channels by electrophysiology and further evaluated on sustained neuronal firing and on in vitro epileptiform activity using a high K<sup>+<\/sup>\u2010low Ca<sup>2+<\/sup>\u00a0model in hippocampal slices. Results: We identified a novel compound able to modulate the interaction of the KV1.1\/KV\u03b21 complex and that produced a functional inhibition of KV1.1\/KV\u03b21 channel inactivation. We demonstrated that this compound reduced the sustained repetitive firing in hippocampal neurons and was able to abolish the development of in vitro epileptiform activity. Conclusions: This study describes a rational drug discovery approach for the identification of novel ligands that inhibit KV1.1 channel inactivation and provides pharmacological evidence that such a mechanism translates into physiological effects by reducing in vitro epileptiform activity.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[55],"target_categories":[61],"target_families":[333],"targets":[248],"resource_keyword":[],"class_list":["post-6305","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cns","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv1-1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6305","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6305"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6305"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6305"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6305"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6305"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6305"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6305"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6305"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6305"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}