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- W2065963898 abstract "σ receptors represent a potential drug target for numerous therapeutic indications including cancer, depression, psychostimulant abuse, and stroke. Most published radioligand binding studies for σ receptors utilize a low throughput method employing a “cell harvester.” Higher throughput methods are required to facilitate efficient screening of large numbers of novel compounds. In this study, a series of reference compounds was analyzed with a new medium-throughput 96-well filtration method and the results were compared to those obtained using the conventional cell harvester-based method. The 96-well assay utilized rat liver membranes for the determination of both known σ receptor subtypes (σ 1 and σ 2 ) because this tissue contains high densities of both subtypes and fulfills criteria required for reliable use with the 96-well format. The new method gave comparable K i values for reference ligands analyzed in parallel with samples prepared in rat brain membranes and processed on the traditional cell harvester. For σ 1 receptors, equivalent affinity values were observed for both methods/tissues. For σ 2 receptors, approximately 2-fold higher affinities were observed for most compounds in liver, as compared to brain membranes, but excellent correlation with brain-derived values was maintained. To further demonstrate the utility of the new method it was used to screen a novel series of 2(3H)-benzothiazolone compounds, resulting in the identification of several analogues with nanomolar affinity and greater than 50-fold specificity for σ 1 versus σ 2 receptors." @default.
- W2065963898 created "2016-06-24" @default.
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- W2065963898 date "2012-12-01" @default.
- W2065963898 modified "2023-09-27" @default.
- W2065963898 title "A 96-well filtration method for radioligand binding analysis of σ receptor ligands" @default.
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- W2065963898 doi "https://doi.org/10.1016/j.jpba.2012.07.023" @default.
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