Drug discovery in the pharmaceutical and biotechnology companies has seen spectacular changes in the last decade mainly due to technological advances in biology, biochemical assays, genomics, proteomics, combinatorial chemistry, miniaturization, automation, computerization, and information technologies. With this technological revolution, drug screening capacities have increased immensely, allowing the pharmaceutical companies to process an increased number of drug targets rapidly by miniaturization and automation using robots for screening the large compound decks and combinatorial compound libraries. To bring a drug to market quickly by reducing the time taken from the target identification to the drug development, pharmaceutical companies have been implementing an assembly-line approach by automation of drug screening.

The screen paradigm is given in Figure 1. From the time a target is selected to screening the compound deck involves the development of assays, optimization of assays, screen development, optimization, and validation before screening the compound deck. The goal of screening groups is to generate a large number of hit compounds that can be advanced to lead compounds that will be further advanced to pre-clinical and clinical development [1]. The aim of the pharmaceutical companies is to achieve first-in-class or best-in-class drugs so that they may become blockbuster drugs. This mandates quality screens and compound decks that enable the generation of quality hits. The screening groups implementing innovative screening technologies, by the use of robots, novel assays, and new miniaturized screening formats, may create a technology gap between the screening groups and the therapeutic area [2]. If the assays developed in therapeutic

Screen Paradigm

Screen Paradigm

Figure 1 Screen paradigm. General lead generation organizational structure in big Pharma is given here. The target selection, developing assay reagents, and assay development and optimization are usually done in the therapeutic areas in consultation with an HTS group. The therapeutic area transfers the assay to a centralized HTS group where the assay and target priority are reviewed. From the assay transferred a screen is developed and validated. The screen is automated and optimized and then run against the large compound deck (compound collection), which will result in lead generation. Leads will be confirmed, and the dose-response for those will be determined. Lead information is sent to the therapeutic area for followup on the leads.

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