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• W2059366971 abstract "The ability of high throughput membrane binding assays to detect ligands for G-protein coupled receptors was examined using mathematical models. Membrane assay models were developed using the extended ternary complex model (Samama et al., 1993) as a basis. Ligand binding to whole cells was modeled by adding a G-protein activation step. Results show that inverse agonists bind more slowly and with a lower affinity to receptors in the membrane binding assay than to receptors in whole cells, causing the membrane assay to miss pharmaceutically important inverse agonists. Assay modifications to allow detection of inverse agonists are discussed. Finally, kinetic binding data are shown to provide information about ligand efficacy. This work demonstrates the utility of mathematical modeling in detecting biases in drug-screening assay, and also in suggesting techniques to correct those biases." @default.
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• W2059366971 date "2001-02-01" @default.
• W2059366971 modified "2023-09-28" @default.
• W2059366971 title "Uncovering Biases in High Throughput Screens of G-Protein Coupled Receptors" @default.
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• W2059366971 doi "https://doi.org/10.1006/jtbi.2000.2227" @default.
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