{"id":6590,"date":"2023-02-17T07:01:03","date_gmt":"2023-02-17T07:01:03","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2022-automated-patch-clamp-screening-of-amiloride-and-5-nn-hexamethyleneamiloride-hma-analogs-identifies-6-iodoamiloride-as-a-potent-acid-sensing-ion-channel-inhibitor\/"},"modified":"2023-06-07T10:08:00","modified_gmt":"2023-06-07T10:08:00","slug":"2023-automated-patch-clamp-screening-of-amiloride-and-5-nn-hexamethyleneamiloride-hma-analogs-identifies-6-iodoamiloride-as-a-potent-acid-sensing-ion-channel-inhibitor","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2023-automated-patch-clamp-screening-of-amiloride-and-5-nn-hexamethyleneamiloride-hma-analogs-identifies-6-iodoamiloride-as-a-potent-acid-sensing-ion-channel-inhibitor\/","title":{"rendered":"2023 &#8211; Automated Patch Clamp Screening of Amiloride and 5-N,N-Hexamethyleneamiloride Analogs Identifies 6-Iodoamiloride as a Potent Acid-Sensing Ion Channel Inhibitor"},"content":{"rendered":"<p>Acid-sensing ion channels (ASICs) are transmembrane sensors of extracellular acidosis and potential drug targets in several disease indications, including neuropathic pain and cancer metastasis. The K<sup>+<\/sup>-sparing diuretic amiloride is a moderate nonspecific inhibitor of ASICs and has been widely used as a probe for elucidating ASIC function. In this work, we screened a library of 6-substituted and 5,6-disubstituted amiloride analogs using a custom-developed automated patch clamp protocol and identified 6-iodoamiloride as a potent ASIC1 inhibitor. Follow-up IC<sub>50<\/sub>\u00a0determinations in tsA-201 cells confirmed higher ASIC1 inhibitory potency for 6-iodoamiloride\u00a0<b>94<\/b>\u00a0(hASIC1\u00a0<b>94<\/b>\u00a0IC<sub>50<\/sub>\u00a0= 88 nM, cf. amiloride\u00a0<b>11<\/b>\u00a0IC<sub>50<\/sub>\u00a0= 1.7 \u03bcM). A similar improvement in activity was observed in ASIC3-mediated currents from rat dorsal root ganglion neurons (rDRG single-concentration\u00a0<b>94<\/b>\u00a0IC<sub>50<\/sub>\u00a0= 230 nM, cf.\u00a0<b>11<\/b>\u00a0IC<sub>50<\/sub>\u00a0= 2.7 \u03bcM). 6-Iodoamiloride represents the amiloride analog of choice for studying the effects of ASIC inhibition on cell physiology.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42,44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[56,57],"target_categories":[337],"target_families":[368],"targets":[105,138],"resource_keyword":[],"class_list":["post-6590","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","therapeutic_areas-pain","therapeutic_areas-cancer","target_categories-ligand-gated-ion-channels","target_families-asic-channels","targets-asic3","targets-asic1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6590","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=6590"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6590"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6590"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6590"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6590"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6590"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6590"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6590"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6590"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}