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The role of drug transporters in phenotypic screening

The relative failure of molecular target-based drug discovery has led to a return to phenotypic screening. Targets that are intracellular necessitate their drug ligands to pass through plasma membranes, where the protein:lipid ratio is often 3:1 by mass and at least 1:1 by area. The widespread view that most of such transmembrane drug transport occurs through the phospholipid bilayer portion is incorrect: drugs must and do exploit transmembrane protein transporters that have been selected or evolved for the uptake of intermediary metabolites and natural products.











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