{"id":6675,"date":"2023-02-17T07:15:27","date_gmt":"2023-02-17T07:15:27","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2022-translating-the-measurement-of-herg-kinetics-and-drug-block-for-cipa-to-a-high-throughput-platform\/"},"modified":"2023-02-17T07:15:27","modified_gmt":"2023-02-17T07:15:27","slug":"2022-translating-the-measurement-of-herg-kinetics-and-drug-block-for-cipa-to-a-high-throughput-platform","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2022-translating-the-measurement-of-herg-kinetics-and-drug-block-for-cipa-to-a-high-throughput-platform\/","title":{"rendered":"2022 &#8211; Translating the Measurement of Herg Kinetics and Drug Block for Cipa to a High Throughput Platform"},"content":{"rendered":"<p>The Comprehensive in vitro Proarrhythmic Assay (CiPA) has promoted use of in silico models of drug\u00a0effects on cardiac repolarization to improve proarrhythmic risk prediction. These models contain a\u00a0pharmacodynamic component describing drug binding to hERG channels that required in vitro data\u00a0for kinetics of block, in addition to potency, to constrain them. To date, development and validation\u00a0has been undertaken using data from manual patch-clamp. To enable the application of this approach\u00a0at scale this requires the development of a high-throughput, automated patch-clamp (APC)\u00a0implementation. Here, we present a comprehensive analysis of the implementation of the Milnes, or CiPA dynamic protocol, on an APC platform, including automated quality control and data analysis.\u00a0Kinetics and potency of block were assessed for bepridil, cisapride, terfenadine and verapamil\u00a0with data retention\/QC pass rate of 21.8%. The variability in IC<sub>50<\/sub> and kinetics between manual and\u00a0APC was comparable to that seen between sites\/platforms in previous APC studies of potency. Whilst\u00a0the experimental success is less than observed in screens of potency alone, it is still significantly\u00a0greater than manual patch. With appropriate consideration of protocol design, including sweep\u00a0length, number of repetitions, and leak correction, this protocol can be applied on APC to acquire data\u00a0comparable to manual patch clamp.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[54],"target_categories":[61],"target_families":[333],"targets":[92],"resource_keyword":[],"class_list":["post-6675","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv11-1-herg"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6675","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=6675"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6675"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6675"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6675"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6675"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6675"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6675"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6675"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6675"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}