A. Cell-Based vs. Mechanism-Based Screens
Cell-based screening, in which an intact cell is used to measure a particular response, had been a primary screening strategy prior to the broad use of recombinant technologies. Recombinant technology has made reagents readily available for use in assays as components of the cell and thus facilitated the focus on mechanism-based or target-based screening. This allowed for a focused approach targeting specific biological molecules. One could define the potency of a new drug at a molecular interaction site and reduce nonspecific side effects. A disadvantage of mechanism-based screening, however, is that a cell pathway or cell function may be known but the precise molecular target may be unclear. In addition, target-based screening does not take into account cell permeability, and while this is not disadvantageous for cell-surface targets, this issue is substantive
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