{"id":17323,"date":"2025-05-12T09:14:30","date_gmt":"2025-05-12T09:14:30","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=17323"},"modified":"2025-05-12T09:14:30","modified_gmt":"2025-05-12T09:14:30","slug":"2025-comparative-analysis-of-the-single-molecule-transport-kinetics-of-oatp1b1-genetic-variants","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2025-comparative-analysis-of-the-single-molecule-transport-kinetics-of-oatp1b1-genetic-variants\/","title":{"rendered":"2025 &#8211; Comparative analysis of the single-molecule transport kinetics of OATP1B1 genetic variants"},"content":{"rendered":"<p>Several genetic variants of OATP1B1, a hepatic uptake transporter, increase the blood concentrations of substrate drugs, e.g., \u221715 carriers exhibit higher blood substrate concentrations than \u22171b carriers. It remains unclear whether these differences are due to changes in expression or intrinsic activity (transport activity per OATP1B1 molecule). This study compared the intrinsic activity of four OATP1B1 variants, \u22171a, \u22171b, \u22175, and \u221715, using HEK293\u00a0cell lines that co-expressed large-conductance Ca<sup>2+<\/sup>-activated K<sup>+<\/sup>\u00a0(BK) channels and one of the OATP1B1 variants. To estimate the kinetic parameters\u00a0<em>K<\/em><sub>m<\/sub>\u00a0and\u00a0<em>V<\/em><sub>max<\/sub>, 2\u2032, 7\u2032-dichlorofluorescein uptake was evaluated. The number of OATP molecules per cell (Q<sub>T<\/sub>) was calculated from BK channel-mediated whole-cell conductance and the OATP1B1\/BK channel expression ratio (\u03c1) (determined by LC-MS\/MS).\u00a0<em>V<\/em><sub>max,int<\/sub>\u00a0(maximum intrinsic transport velocity) was obtained by dividing\u00a0<em>V<\/em><sub>max<\/sub>\u00a0by Q<sub>T<\/sub>, and intrinsic clearance (<em>CL<\/em><sub>int<\/sub>) was calculated as\u00a0<em>V<\/em><sub>max,int<\/sub>\/<em>K<\/em><sub>m<\/sub>. The\u00a0<em>K<\/em><sub>m<\/sub>\u00a0values of \u22171a, \u22171b, \u22175, and \u221715 were 12.5, 9.19, 7.53, and 10.4\u00a0\u03bcM, and their\u00a0<em>V<\/em><sub>max,int<\/sub>\u00a0values were 3.0, 7.0, 1.5, and 1.2\u00a0\u00d7\u00a010<sup>\u221221<\/sup>\u00a0mol\/OATP molecule\/min, respectively. Accordingly, the\u00a0<em>CL<\/em><sub>int<\/sub>\u00a0value for OATP1B1\u221715 was 15 % lower than that for OATP1B1\u22171b, suggesting that the increased blood substrate concentrations observed in OATP1B1\u221715 carriers may be due to the decreased intrinsic activity of OATP1B1\u221715.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[53,108],"therapeutic_areas":[143],"target_categories":[60],"target_families":[507],"targets":[508],"resource_keyword":[],"class_list":["post-17323","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-assay-development-and-validation","application_areas-transporters","therapeutic_areas-assay-development-and-validation","target_categories-transporters","target_families-organo-anion-transporter-family","targets-oatp1b1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/17323","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=17323"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=17323"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=17323"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=17323"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=17323"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=17323"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=17323"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=17323"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=17323"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}