{"id":6556,"date":"2023-02-17T06:57:57","date_gmt":"2023-02-17T06:57:57","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-suppressing-kv1-3-ion-channel-activity-with-a-novel-small-molecule-inhibitor-ameliorates-inflammation-in-a-humanised-mouse-model-of-ulcerative-colitis\/"},"modified":"2023-02-17T06:57:57","modified_gmt":"2023-02-17T06:57:57","slug":"2021-suppressing-kv1-3-ion-channel-activity-with-a-novel-small-molecule-inhibitor-ameliorates-inflammation-in-a-humanised-mouse-model-of-ulcerative-colitis","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-suppressing-kv1-3-ion-channel-activity-with-a-novel-small-molecule-inhibitor-ameliorates-inflammation-in-a-humanised-mouse-model-of-ulcerative-colitis\/","title":{"rendered":"2021 &#8211; Suppressing KV1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis"},"content":{"rendered":"<p>Background and Aims:\u00a0The potassium channel KV1.3 is a potentially attractive therapeutic target\u00a0in T cell-mediated inflammatory diseases, as the activity of antigen-activated T cells is selectively\u00a0impeded by KV1.3 inhibition. In this study, we examined KV1.3 as a potential therapeutic intervention\u00a0point for ulcerative colitis [UC], and studied the efficacy of DES1, a small-molecule inhibitor of\u00a0KV1.3, in vitro and in vivo.Methods:\u00a0KV1.3 expression on T cells in peripheral blood mononuclear cells [PBMCs] isolated from donors with and without UC was examined by flow cytometry. In biopsies from UC patients, KV1.3-expressing CD4+ T cells were detected by flow cytometry and immunohistochemistry. In vitro, we determined the ability of DES1 to inhibit anti-CD3-driven activation of T cells. In vivo, the efficacy of DES1 was determined in a humanised mouse model of UC and compared with infliximab and tofacitinib in head-to-head studies.Results:\u00a0KV1.3 expression was elevated in PBMCs from UC patients and correlated with the prevalence of TH1 and TH2 T cells. KV1.3 expression was also detected on T cells from biopsies of UC patients. In vitro, DES1 suppressed anti-CD3-driven activation of T cells in a concentration-dependent manner. In vivo, DES1 significantly ameliorated inflammation in the UC model and most effectively so when PBMCs from donors with higher levels of activated T cells were selected for reconstitution. The efficacy of DES1 was comparable to that of either infliximab or tofacitinib.Conclusion:\u00a0Inhibition of KV1.3 [by DES1, for instance] appears to be a potential therapeutic intervention strategy for UC patients.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[61],"target_families":[333],"targets":[115],"resource_keyword":[],"class_list":["post-6556","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv1-3"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6556","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=6556"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6556"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6556"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6556"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6556"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6556"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6556"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6556"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6556"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}