Discovery research testing

As Kinter et al. (1994) reported, in many pharmacological laboratories prior to 1990, organ function testing was often conducted as an ancillary function of discovery research. The selection of specific studies for a candidate drug was based on concerns raised from its primary (those pharmacodynamic effects related to... 

Figure 15.2 illustrates some of the discovery bioactivity experiments in which a test compound must be successful to advance. If erroneous activity or selectivity data are generated or misinterpreted, the SAR will mislead the project team. SAR is a central strategy of drug-discovery research. If the activity assays are affected by properties in addition to target protein interaction, then the SAR will be a composite of multiple variables. Table 15.1 lists some of the potential effects on SAR from lack of property data application in planning and interpretation of drug-discovery bioassays. 

The National Institutes of Health conducts targeted drug discovery and testing programs. The transfer of the scientific knowledge with commercial value from this agency to the pharmaceutical industry is one of the ways that pharmaceutical companies directly benefit from Federal research support. 

Figure 1 Change of the synthesis-and-testing paradigm in drug discovery research, (a) Classical situation where compound (from left to right) and data flows (right to left) are balanced, (b) Increase in synthesis and testing capacities increased data and compound flows, (c) Further increase of data flow due to increased profiling activities and introduction of data mining as a tool to extract information and knowledge.

Most of the studies with these alternative models were conducted in discovery research. However, several respondents had conducted pivotal regulatory toxicity studies with homologous proteins and animal disease models, either to allow products such as MAbs and cytokines to be tested in man, or in support of regulatory toxicity studies by clarifying a finding. Only one respondent had conducted pivotal regulatory toxicity studies with transgenic animals in order to take a MAb into man. 

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