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Cell-based apoptosis assays in oncology drug discovery

Importance of the field: Screening compounds with a cell-based phenotypic approach complements target-based discovery programs because of the opportunity to investigate targets in the context of the cellular milieu and to discover novel targets. Areas covered in this review: Utilizing a cell-based apoptotic phenotype screen for discovery and optimization of apoptosis inducers and affirming activity as potential anticancer agents in vivo with xenograft models. Subsequently, chemical genetic tools are utilized to identify and validate previously unrecognized cancer targets. Case studies showing the various multidisciplinary approaches utilized for several years are reviewed. What the reader will gain: The interactive nature of the drug and target discovery processes, and insights that come from integration of cellular biology, medicinal chemistry and animal research. Take home message: Phenotype proapoptotic screen followed by chemical genetics is useful for anticancer drug research, for the discovery of potential drugs and identification of druggable targets.