{"id":6206,"date":"2023-02-17T07:02:54","date_gmt":"2023-02-17T07:02:54","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2017-prolonged-immunomodulation-in-inflammatory-arthritis-using-the-selective-kv1-3-channel-blocker-hstx1r14a-and-its-pegylated-analog\/"},"modified":"2023-02-17T07:02:55","modified_gmt":"2023-02-17T07:02:55","slug":"2017-prolonged-immunomodulation-in-inflammatory-arthritis-using-the-selective-kv1-3-channel-blocker-hstx1r14a-and-its-pegylated-analog","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2017-prolonged-immunomodulation-in-inflammatory-arthritis-using-the-selective-kv1-3-channel-blocker-hstx1r14a-and-its-pegylated-analog\/","title":{"rendered":"2017 &#8211; Prolonged immunomodulation in inflammatory arthritis using the selective KV1.3 channel blocker HsTX1[R14A] and its PEGylated analog"},"content":{"rendered":"<p>Effector memory T lymphocytes (TEM\u00a0cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The KV1.3 potassium channel is a key regulator of CCR7\u2212\u00a0TEM\u00a0cell activation. Blocking KV1.3 inhibits TEM\u00a0cell activation and attenuates inflammation in autoimmunity, and as such, KV1.3 has emerged as a promising target for the treatment of TEM\u00a0cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent KV1.3 blockers and HsTX1[R14A] is selective for KV1.3 over closely-related KV1 channels. PEGylation of HsTX1[R14A] to create a KV1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for KV1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7\u2212\u00a0TEM\u00a0cell proliferation, leaving CCR7+\u00a0na\u00efve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM\u00a0cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[56,113],"target_categories":[61],"target_families":[333],"targets":[115,249],"resource_keyword":[],"class_list":["post-6206","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-pain","therapeutic_areas-immune-diseases","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv1-3","targets-kv1-5"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6206","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=6206"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6206"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6206"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6206"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6206"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6206"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6206"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6206"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6206"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}