ABSTRACT
The identification of a cellular or molecular target for drug discovery and the development and validation of a relevant bioassay are critical early milestones in an HTS program. There must be a persuasive reason to believe that the cellular or molecular (enzyme, receptor, protein-protein, or protein-DNA interaction) target is involved in a pivotal step in the targeted disease process. That link-the molecular target to the disease process-requires exhaustive analysis. Today with the cost of screening at $3-5 per well (compound and reagents) at the 96-well plate level, the assessment of a 50,000-member library will cost as much as $250,000 before personnel costs and overhead are considered. Many of us can recount pre-HTS times when certain animal or biochemical assays formed the core of a discovery program only to prove of little or no value in the identification of a clinically active agent. Relevance must be carefully balanced against cost (Fig. 4).
