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ing assays, and (2) cell-based assays. The assays in these two groups may be either heterogeneous or homogeneous types. The traditional assays about two decades before were single tube analytical assays with low throughput. Although the compound deck size was relatively small, the screening of each target took several months, and screening groups were able to handle only a handful of screens. The gradual transformation of screening to the plate format and improved engineering, spectroscopic, and biochemical techniques enabled workers to develop very sensitive homogeneous and heterogeneous assays with increased throughput and automation of the screening, allowing them to screen increased sizes of compound libraries, with reductions in the costs of materials and screening time. With the development of highly sensitive assays and the availability of higher density plates and sensitive plate readers that can read high-density plates, screening is progressing to uHTS.

IV. IN VITRO (CELL-FREE) ASSAYS

Cell-free assays include simple to very complex systems (Fig. 3). These biochemical assays include enzyme assays, protein-protein interactions, and membrane receptor-ligand and soluble receptor-ligand binding assays. The advantages of in vitro biochemical screening include more ready accessibility of the compounds

Figure 3 Cell-free biochemical assays. The in vitro assays are mainly classified into heterogeneous and homogeneous assays and subdivided into radioactive and nonradio-active assays.

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