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Fundamental processes in living cells, such as apoptosis and signal transduction are controlled by proteins, often acting in concert with other protein partners through protein-protein interactions (PPIs). Inappropriate protein-protein recognition can fundamentally contribute to many diseases, including cancer. Therefore, inhibiting protein-protein interactions represents an emerging area in drug design.
Analyzing transport of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. A functional impairment of hepatobilary transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP-2), is strongly associated with an increased risk of cholestatic liver injury. Here, we describe a 3D high-content screening assay to study hepatobiliary transporter function in InSphero human liver microtissues. Confocal imaging and automated image analysis were used to quantify BSEP and MRP-2-mediated efflux of fluorescent substrates into bile canaliculi.
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