During the last few years, it has become apparent that cell-based screens provide significant advantages in that hits identified in these screens can be rapidly developed into drugs [2,3] (Fig. 1). Moreover, as there are many thousands of targets in a cell, hits in a cell-based screen show some degree of selectivity towards the target or they would not be detected in the screen. Hits from a cell-based screen can be shown to have activity in the cell where the target is naturally expressed. Such hits face little delay in moving into lead optimization for preclinical candidate identification. Once the activity of the hits is confirmed in secondary assays, chemical modifications can be focused on optimization of potency and pharmaceutical properties (Fig. 2).
Although many enzymes can be cloned and expressed to produce large amounts of protein, it is not always feasible to provide sufficient amounts of
Figure 1 Back to the future: Cell-based screening systems are gaining in popularity because of the quality of the leads generated from these screens and the high information content of cell-based screens.
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