Target Based Screening

Molecular biology has provided the tools to engineer and produce macromolecular targets of drug action. If it is believed that the inhibition of a particular cell-signaling process will mediate the development of disease, then the isolated enzyme, or receptor that is responsible for the signaling can be used as a target for screening. Alternatively, a selective whole cell screen can be employed that is designed to respond by providing some measurable signal as a result of the interaction with a particular target. Owing to developments in automation for such assay systems, hundreds of thousands of compounds can be conveniently tested for activity in a short period of time. Natural product mixtures may also be tested in these highly automated systems. With mixtures, particularly crude extracts, there is the potential for significant interference with the assay. Such interferences include nonspecific inhibition of targets by ubiquitous classes of natural products like fatty acids, or the presence of a highly potent cytotoxic agent that kills the host cell designed for the specific assay. These issues are not insurmountable, but require diligence in evaluating screening results. Some solutions for these issues are presented in Section 6.4.5.

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