High-throughput screening filters

Figure 4.10 Hit progression scheme for compounds identified from high-throughput screening. Note that the specific sequence of activities may vary from one organization to another, or even from one project to another, depending on practical considerations. For example, the location within the sequence of the chemical tractability filter may come before or after confirmation of reproducibility.

Caco-2 cells in high-throughput screening for NCEs in the pharmaceutical industry has increased tremendously. The utility of this monolayer model to either rank order or filter out compounds has been exemplified by many previous studies [10, 11],... 

Such examples extend PBPK simulations to prediction of target effect and appear very powerful for generation of insights into the efficacy/lack of efficacy in vivo in relation to receptor occupancy. Consequently, such PBPK/PD simulations can be used as a filter between high-throughput screening and in vivo efficacy in order to prioritize compounds expected to be active in vivo. 

Figure 2. High-throughput screening provides a broader funnel and additional filters at the front end of conventional catalyst research.

Pearce, B. C., Sofia, M. J., Good, A. C., Drexler, D. M., Stock, D. A. An empirical process for the design of high-throughput screening deck filters. J. Chem. Inform. Model 2006, 46, 1060-1068. 

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