Assay Development High Throughput or In Vitro Cell Panels

High-volume screening in vitro is a critical aspect of the lead selection and drug development process (Figures 1 and 2) initially started with the development of nitrogen mustard derivatives in 1946, as reviewed by Dendy and Hill.5 Until 1985, for the most part screening was performed in vivo. Around this time the National Cancer Institute (NCI) initiated a program for improving anticancer drug discovery6; they deployed an empirical scheme based on an initial three-cell line prescreen panel, followed by a 60-cell line screen. For compounds with significant (cytotoxic) activity, the drug would probably be evaluated in the hollow-fiber (HF) assay (in vivo model) developed by Hollingshead et al. This approach was or is predominantly used for the discovery of antiproliferative and cytotoxic drugs, but for the drugs that target signal transduction pathway, small molecules, static (antiangiogenic) drugs, and antibodies, the need for both biochemical 'target-driven' screening assays and tailored cellular screens became evident. For these agents, the use of cell-free target-specific, high-throughput screening (HTS) using miniaturization, robot-aided automation, and data management allowed large libraries of compounds to be tested efficiently.8 An indepth review of HTS and current assay strategies can be found in the Anticancer Drug Development Guide?

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