{"id":6475,"date":"2023-02-17T07:08:33","date_gmt":"2023-02-17T07:08:33","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-a-solid-supported-membrane-based-technology-for-electrophysical-screening-of-b0at1-modulating-compounds\/"},"modified":"2023-02-17T07:08:34","modified_gmt":"2023-02-17T07:08:34","slug":"2021-a-solid-supported-membrane-based-technology-for-electrophysical-screening-of-b0at1-modulating-compounds","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-a-solid-supported-membrane-based-technology-for-electrophysical-screening-of-b0at1-modulating-compounds\/","title":{"rendered":"2021 &#8211; A Solid Supported Membrane-Based Technology for Electrophysical Screening of B0AT1-Modulating Compounds"},"content":{"rendered":"<p>Classical high-throughput screening (HTS) technologies for the analysis of ionic currents across biological membranes\u00a0can be performed using fluorescence-based, radioactive, and mass spectrometry (MS)-based uptake assays. These assays\u00a0provide rapid results for pharmacological HTS, but the underlying, indirect analytical character of these assays can be linked\u00a0to high false-positive hit rates. Thus, orthogonal and secondary assays using more biological target-based technologies are\u00a0indispensable for further compound validation and optimization. Direct assay technologies for transporter proteins are\u00a0electrophysiology-based, but are also complex, time-consuming, and not well applicable for automated profiling purposes.\u00a0In contrast to conventional patch clamp systems, solid supported membrane (SSM)-based electrophysiology is a sensitive,\u00a0membrane-based method for transporter analysis, and current technical developments target the demand for automated,\u00a0accelerated, and sensitive assays for transporter-directed compound screening. In this study, the suitability of the SSM based technique for pharmacological compound identification and optimization was evaluated performing cell-free SSMbased measurements with the electrogenic amino acid transporter B0AT1 (SLC6A19). Electrophysiological characterization\u00a0of leucine-induced currents demonstrated that the observed signals were specific to B0AT1. Moreover, B0\u00a0AT1-dependent\u00a0responses were successfully inhibited using an established in-house tool compound. Evaluation of current stability and\u00a0data reproducibility verified the robustness and reliability of the applied assay. Active compounds from primary screens\u00a0of large compound libraries were validated, and false-positive hits were identified. These results clearly demonstrate the\u00a0suitability of the SSM-based technique as a direct electrophysiological method for rapid and automated identification of\u00a0small molecules that can inhibit B0AT1 activity<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36,132],"resource_type":[75],"application_areas":[53,108],"therapeutic_areas":[],"target_categories":[60],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6475","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","products_tags-surfe2r-96se","resource_type-publication","application_areas-assay-development-and-validation","application_areas-transporters","target_categories-transporters"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6475","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=6475"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6475"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6475"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6475"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6475"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6475"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6475"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6475"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6475"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}